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Lipid Mediators in Inflammation

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  • Authors: Melanie Bennett1, Derek W. Gilroy2
  • Editor: Siamon Gordon3
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Roche Products Limited, Shire Park, Welwyn Garden City AL7 1TW, United Kingdom; 2: Centre for Clinical Pharmacology and Therapeutics, Division of Medicine, University College London, London WC1 E6JJ, United Kingdom; 3: Oxford University, Oxford, United Kingdom
  • Source: microbiolspec November 2016 vol. 4 no. 6 doi:10.1128/microbiolspec.MCHD-0035-2016
  • Received 18 May 2016 Accepted 26 September 2016 Published 11 November 2016
  • Derek W. Gilroy, d.gilroy@ucl.ac.uk
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  • Abstract:

    Lipids are potent signaling molecules that regulate a multitude of cellular responses, including cell growth and death and inflammation/infection, via receptor-mediated pathways. Derived from polyunsaturated fatty acids (PUFAs), such as arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), each lipid displays unique properties, thus making their role in inflammation distinct from that of other lipids derived from the same PUFA. This diversity arises from their synthesis, which occurs via discrete enzymatic pathways and because they elicit responses via different receptors. This review will collate the bioactive lipid research to date and summarize the major pathways involved in their biosynthesis and role in inflammation. Specifically, lipids derived from AA (prostanoids, leukotrienes, 5-oxo-6,8,11,14-eicosatetraenoic acid, lipoxins, and epoxyeicosatrienoic acids), EPA (E-series resolvins), and DHA (D-series resolvins, protectins, and maresins) will be discussed herein.

  • Citation: Bennett M, Gilroy D. 2016. Lipid Mediators in Inflammation. Microbiol Spectrum 4(6):MCHD-0035-2016. doi:10.1128/microbiolspec.MCHD-0035-2016.

Key Concept Ranking

Chemicals
0.6280828
Mast Cells
0.5779902
Cytokine Growth Factors
0.4859305
Fatty Acids
0.46404606
Lipids
0.45019877
Signalling Pathway
0.43366152
0.6280828

References

1. Serhan C, Ward P, Gilroy D. 2010. Fundamentals of Inflammation. Cambridge University Press, Cambridge, United Kingdom. [CrossRef]
2. Segal AW. 2005. How neutrophils kill microbes. Annu Rev Immunol 23:197–223. [CrossRef]
3. Serhan CN, Savill J. 2005. Resolution of inflammation: the beginning programs the end. Nat Immunol 6:1191–1197. [CrossRef]
4. Majno G, Joris I. 2004. Cells, Tissues and Disease: Principles of General Pathology, 2nd ed. Oxford University Press, New York, NY.
5. Buckley CD, Gilroy DW, Serhan CN. 2014. Proresolving lipid mediators and mechanisms in the resolution of acute inflammation. Immunity 40:315–327. [CrossRef]
6. Buckley CD, Gilroy DW, Serhan CN, Stockinger B, Tak PP. 2013. The resolution of inflammation. Nat Rev Immunol 13:59–66. [CrossRef]
7. Segal AW, Geisow M, Garcia R, Harper A, Miller R. 1981. The respiratory burst of phagocytic cells is associated with a rise in vacuolar pH. Nature 290:406–409. [CrossRef]
8. Gilroy DW, Colville-Nash PR, McMaster S, Sawatzky DA, Willoughby DA, Lawrence T. 2003. Inducible cyclooxygenase-derived 15deoxyΔ12–14PGJ2 brings about acute inflammatory resolution in rat pleurisy by inducing neutrophil and macrophage apoptosis. FASEB J 17:2269–2271.
9. Nibbs RJ, Graham GJ. 2013. Immune regulation by atypical chemokine receptors. Nat Rev Immunol 13:815–829. [CrossRef]
10. Ariel A, Fredman G, Sun YP, Kantarci A, Van Dyke TE, Luster AD, Serhan CN. 2006. Apoptotic neutrophils and T cells sequester chemokines during immune response resolution through modulation of CCR5 expression. Nat Immunol 7:1209–1216. [CrossRef]
11. Piper P, Vane J. 1971. The release of prostaglandins from lung and other tissues. Ann N Y Acad Sci 180:363–385. [CrossRef]
12. Samuelsson B, Dahlén SE, Lindgren JA, Rouzer CA, Serhan CN. 1987. Leukotrienes and lipoxins: structures, biosynthesis, and biological effects. Science 237:1171–1176. [CrossRef]
13. Serhan CN, Hamberg M, Samuelsson B. 1984. Trihydroxytetraenes: a novel series of compounds formed from arachidonic acid in human leukocytes. Biochem Biophys Res Commun 118:943–949. [CrossRef]
14. Capdevila JH, Falck JR, Dishman E, Karara A. 1990. Cytochrome P-450 arachidonate oxygenase. Methods Enzymol 187:385–394. [CrossRef]
15. Pagels WR, Sachs RJ, Marnett LJ, Dewitt DL, Day JS, Smith WL. 1983. Immunochemical evidence for the involvement of prostaglandin H synthase in hydroperoxide-dependent oxidations by ram seminal vesicle microsomes. J Biol Chem 258:6517–6523.
16. Hamberg M, Samuelsson B. 1973. Detection and isolation of an endoperoxide intermediate in prostaglandin biosynthesis. Proc Natl Acad Sci U S A 70:899–903. [CrossRef]
17. Nugteren DH, Hazelhof E. 1973. Isolation and properties of intermediates in prostaglandin biosynthesis. Biochim Biophys Acta 326:448–461. [CrossRef]
18. Dubois RN, Abramson SB, Crofford L, Gupta RA, Simon LS, Van De Putte LB, Lipsky PE. 1998. Cyclooxygenase in biology and disease. FASEB J 12:1063–1073.
19. Shimizu T, Yamamoto S, Hayaishi O. 1982. Purification of PGH-PGD isomerase from rat brain. Methods Enzymol 86:73–77. [CrossRef]
20. Tanaka Y, Ward SL, Smith WL. 1987. Immunochemical and kinetic evidence for two different prostaglandin H-prostaglandin E isomerases in sheep vesicular gland microsomes. J Biol Chem 262:1374–1381.
21. Hayashi H, Fujii Y, Watanabe K, Urade Y, Hayaishi O. 1989. Enzymatic conversion of prostaglandin H2 to prostaglandin F by aldehyde reductase from human liver: comparison to the prostaglandin F synthetase from bovine lung. J Biol Chem 264:1036–1040.
22. DeWitt DL, Smith WL. 1983. Purification of prostacyclin synthase from bovine aorta by immunoaffinity chromatography. Evidence that the enzyme is a hemoprotein. J Biol Chem 258:3285–3293.
23. Ullrich V, Haurand M. 1983. Thromboxane synthase as a cytochrome P450 enzyme. Adv Prostaglandin Thromboxane Leukot Res 11:105–110.
24. Bezugla Y, Kolada A, Kamionka S, Bernard B, Scheibe R, Dieter P. 2006. COX-1 and COX-2 contribute differentially to the LPS-induced release of PGE2 and TxA2 in liver macrophages. Prostaglandins Other Lipid Mediat 79:93–100. [CrossRef]
25. Naraba H, Murakami M, Matsumoto H, Shimbara S, Ueno A, Kudo I, Oh-ishi S. 1998. Segregated coupling of phospholipases A2, cyclooxygenases, and terminal prostanoid synthases in different phases of prostanoid biosynthesis in rat peritoneal macrophages. J Immunol 160:2974–2982.
26. Jakobsson PJ, Thorén S, Morgenstern R, Samuelsson B. 1999. Identification of human prostaglandin E synthase: a microsomal, glutathione-dependent, inducible enzyme, constituting a potential novel drug target. Proc Natl Acad Sci U S A 96:7220–7225. [CrossRef]
27. Penglis PS, Cleland LG, Demasi M, Caughey GE, James MJ. 2000. Differential regulation of prostaglandin E2 and thromboxane A2 production in human monocytes: implications for the use of cyclooxygenase inhibitors. J Immunol 165:1605–1611. [CrossRef]
28. Brock TG, McNish RW, Peters-Golden M. 1999. Arachidonic acid is preferentially metabolized by cyclooxygenase-2 to prostacyclin and prostaglandin E2. J Biol Chem 274:11660–11666. [CrossRef]
29. Hirai H, Tanaka K, Yoshie O, Ogawa K, Kenmotsu K, Takamori Y, Ichimasa M, Sugamura K, Nakamura M, Takano S, Nagata K. 2001. Prostaglandin D2 selectively induces chemotaxis in T helper type 2 cells, eosinophils, and basophils via seven-transmembrane receptor CRTH2. J Exp Med 193:255–261. [CrossRef]
30. Monneret G, Gravel S, Diamond M, Rokach J, Powell WS. 2001. Prostaglandin D2 is a potent chemoattractant for human eosinophils that acts via a novel DP receptor. Blood 98:1942–1948. [CrossRef]
31. Xue L, Gyles SL, Wettey FR, Gazi L, Townsend E, Hunter MG, Pettipher R. 2005. Prostaglandin D2 causes preferential induction of proinflammatory Th2 cytokine production through an action on chemoattractant receptor-like molecule expressed on Th2 cells. J Immunol 175:6531–6536. [CrossRef]
32. von Euler US. 1936. On the specific vaso-dilating and plain muscle stimulating substances from accessory genital glands in man and certain animals (prostaglandin and vesiglandin). J Physiol 88:213–234. [CrossRef]
33. Eckenfels A, Vane JR. 1972. Prostaglandins, oxygen tension and smooth muscle tone. Br J Pharmacol 45:451–462. [CrossRef]
34. Ferreira SH, Herman A, Vane JR. 1972. Proceedings: prostaglandin generation maintains the smooth muscle tone of the rabbit isolated jejunum. Br J Pharmacol 44:328P–329P.
35. Main IH. 1964. The inhibitory actions of prostaglandins on respiratory smooth muscle. Br Pharmacol Chemother 22:511–519. [CrossRef]
36. Williams TJ. 1979. Prostaglandin E2, prostaglandin I2 and the vascular changes of inflammation. Br J Pharmacol 65:517–524. [CrossRef]
37. Williams TJ, Jose PJ. 1981. Mediation of increased vascular permeability after complement activation. Histamine-independent action of rabbit C5a. J Exp Med 153:136–153. [CrossRef]
38. Ferreira SH, Nakamura M, de Abreu Castro MS. 1978. The hyperalgesic effects of prostacyclin and prostaglandin E2. Prostaglandins 16:31–37. [CrossRef]
39. Feldberg W, Gupta KP. 1973. Pyrogen fever and prostaglandin-like activity in cerebrospinal fluid. J Physiol 228:41–53. [CrossRef]
40. Feldberg W, Saxena PN. 1971. Fever produced by prostaglandin E1. J Physiol 217:547–556. [CrossRef]
41. Milton AS, Wendlandt S. 1971. Effects on body temperature of prostaglandins of the A, E and F series on injection into the third ventricle of unanaesthetized cats and rabbits. J Physiol 218:325–336. [CrossRef]
42. Moncada S, Gryglewski R, Bunting S, Vane JR. 1976. An enzyme isolated from arteries transforms prostaglandin endoperoxides to an unstable substance that inhibits platelet aggregation. Nature 263:663–665. [CrossRef]
43. Kaley G, Hintze TH, Panzenbeck M, Messina EJ. 1985. Role of prostaglandins in microcirculatory function. Adv Prostaglandin Thromboxane Leukot Res 13:27–35.
44. Hata AN, Breyer RM. 2004. Pharmacology and signaling of prostaglandin receptors: multiple roles in inflammation and immune modulation. Pharmacol Ther 103:147–166. [CrossRef]
45. Higgs EA, Moncada S, Vane JR. 1978. Inflammatory effects of prostacyclin (PGI2) and 6-oxo-PGF in the rat paw. Prostaglandins 16:153–162. [CrossRef]
46. Komoriya K, Ohmori H, Azuma A, Kurozumi S, Hashimoto Y, Nicolaou KC, Barnette WE, Magolda RL. 1978. Prostaglandin I2 as a potentiator of acute inflammation in rats. Prostaglandins 15:557–564. [CrossRef]
47. Lewis AJ, Nelson DJ, Sugrue MF. 1975. On the ability of prostaglandin E1, and arachidonic acid to modulate experimentally induced oedema in the rat paw. Br J Pharmacol 55:51–56. [CrossRef]
48. Moncada S, Ferreira SH, Vane JR. 1973. Prostaglandins, aspirin-like drugs and the oedema of inflammation. Nature 246:217–219. [CrossRef]
49. Williams TJ, Morley J. 1973. Prostaglandins as potentiators of increased vascular permeability in inflammation. Nature 246:215–217. [CrossRef]
50. Yuhki K, Ueno A, Naraba H, Kojima F, Ushikubi F, Narumiya S, Oh-ishi S. 2004. Prostaglandin receptors EP2, EP3, and IP mediate exudate formation in carrageenin-induced mouse pleurisy. J Pharmacol Exp Ther 311:1218–1224. [CrossRef]
51. Yuhki K, Ushikubi F, Naraba H, Ueno A, Kato H, Kojima F, Narumiya S, Sugimoto Y, Matsushita M, Oh-Ishi S. 2008. Prostaglandin I2 plays a key role in zymosan-induced mouse pleurisy. J Pharmacol Exp Ther 325:601–609. [CrossRef]
52. Saxena PN, Beg MM, Singhal KC, Ahmad M. 1979. Prostaglandin-like activity in the cerebrospinal fluid of febrile patients. Indian J Med Res 70:495–498.
53. Dantzer R, Konsman JP, Bluthé RM, Kelley KW. 2000. Neural and humoral pathways of communication from the immune system to the brain: parallel or convergent? Auton Neurosci 85:60–65. [CrossRef]
54. Ek M, Kurosawa M, Lundeberg T, Ericsson A. 1998. Activation of vagal afferents after intravenous injection of interleukin-1beta: role of endogenous prostaglandins. J Neurosci 18:9471–9479.
55. Lazarus M, Yoshida K, Coppari R, Bass CE, Mochizuki T, Lowell BB, Saper CB. 2007. EP3 prostaglandin receptors in the median preoptic nucleus are critical for fever responses. Nat Neurosci 10:1131–1133. [CrossRef]
56. Ushikubi F, Segi E, Sugimoto Y, Murata T, Matsuoka T, Kobayashi T, Hizaki H, Tuboi K, Katsuyama M, Ichikawa A, Tanaka T, Yoshida N, Narumiya S. 1998. Impaired febrile response in mice lacking the prostaglandin E receptor subtype EP3. Nature 395:281–284. [CrossRef]
57. Madden CJ, Morrison SF. 2003. Excitatory amino acid receptor activation in the raphe pallidus area mediates prostaglandin-evoked thermogenesis. Neuroscience 122:5–15. [CrossRef]
58. Madden CJ, Morrison SF. 2004. Excitatory amino acid receptors in the dorsomedial hypothalamus mediate prostaglandin-evoked thermogenesis in brown adipose tissue. Am J Physiol Regul Integr Comp Physiol 286:R320–R325. [CrossRef]
59. Morrison SF. 2001. Differential regulation of sympathetic outflows to vasoconstrictor and thermoregulatory effectors. Ann N Y Acad Sci 940:286–298. [CrossRef]
60. Morrison SF. 2003. Raphe pallidus neurons mediate prostaglandin E2-evoked increases in brown adipose tissue thermogenesis. Neuroscience 121:17–24. [CrossRef]
61. Morrison SF. 2004. Central pathways controlling brown adipose tissue thermogenesis. News Physiol Sci 19:67–74. [CrossRef]
62. Ahmadi S, Lippross S, Neuhuber WL, Zeilhofer HU. 2002. PGE2 selectively blocks inhibitory glycinergic neurotransmission onto rat superficial dorsal horn neurons. Nat Neurosci 5:34–40. [CrossRef]
63. Juhlin L, Michaëlsson G. 1969. Cutaneous vascular reactions to prostaglandins in healthy subjects and in patients with urticaria and atopic dermatitis. Acta Derm Venereol 49:251–261.
64. Lin CR, Amaya F, Barrett L, Wang H, Takada J, Samad TA, Woolf CJ. 2006. Prostaglandin E2 receptor EP4 contributes to inflammatory pain hypersensitivity. J Pharmacol Exp Ther 319:1096–1103. [CrossRef]
65. McAdam BF, Mardini IA, Habib A, Burke A, Lawson JA, Kapoor S, FitzGerald GA. 2000. Effect of regulated expression of human cyclooxygenase isoforms on eicosanoid and isoeicosanoid production in inflammation. J Clin Invest 105:1473–1482. [CrossRef]
66. Moriyama T, Higashi T, Togashi K, Iida T, Segi E, Sugimoto Y, Tominaga T, Narumiya S, Tominaga M. 2005. Sensitization of TRPV1 by EP1 and IP reveals peripheral nociceptive mechanism of prostaglandins. Mol Pain 1:3. doi:10.1186/1744-8069-1-3. [CrossRef]
67. Murata T, Ushikubi F, Matsuoka T, Hirata M, Yamasaki A, Sugimoto Y, Ichikawa A, Aze Y, Tanaka T, Yoshida N, Ueno A, Oh-ishi S, Narumiya S. 1997. Altered pain perception and inflammatory response in mice lacking prostacyclin receptor. Nature 388:678–682. [CrossRef]
68. Reinold H, Ahmadi S, Depner UB, Layh B, Heindl C, Hamza M, Pahl A, Brune K, Narumiya S, Müller U, Zeilhofer HU. 2005. Spinal inflammatory hyperalgesia is mediated by prostaglandin E receptors of the EP2 subtype. J Clin Invest 115:673–679. [CrossRef]
69. Solomon LM, Juhlin L, Kirschenbaum MB. 1968. Prostaglandin on cutaneous vasculature. J Invest Dermatol 51:280–282. [CrossRef]
70. Ueno A, Matsumoto H, Naraba H, Ikeda Y, Ushikubi F, Matsuoka T, Narumiya S, Sugimoto Y, Ichikawa A, Oh-ishi S. 2001. Major roles of prostanoid receptors IP and EP3 in endotoxin-induced enhancement of pain perception. Biochem Pharmacol 62:157–160. [CrossRef]
71. Smyth EM, Grosser T, Wang M, Yu Y, FitzGerald GA. 2009. Prostanoids in health and disease. J Lipid Res 50(Suppl):S423–S428. [CrossRef]
72. García Rodríguez LA, Tacconelli S, Patrignani P. 2008. Role of dose potency in the prediction of risk of myocardial infarction associated with nonsteroidal anti-inflammatory drugs in the general population. J Am Coll Cardiol 52:1628–1636. [CrossRef]
73. Grosser T, Fries S, FitzGerald GA. 2006. Biological basis for the cardiovascular consequences of COX-2 inhibition: therapeutic challenges and opportunities. J Clin Invest 116:4–15. [CrossRef]
74. Xiao CY, Hara A, Yuhki K, Fujino T, Ma H, Okada Y, Takahata O, Yamada T, Murata T, Narumiya S, Ushikubi F. 2001. Roles of prostaglandin I2 and thromboxane A2 in cardiac ischemia-reperfusion injury: a study using mice lacking their respective receptors. Circulation 104:2210–2215. [CrossRef]
75. Degousee N, Fazel S, Angoulvant D, Stefanski E, Pawelzik SC, Korotkova M, Arab S, Liu P, Lindsay TF, Zhuo S, Butany J, Li RK, Audoly L, Schmidt R, Angioni C, Geisslinger G, Jakobsson PJ, Rubin BB. 2008. Microsomal prostaglandin E2 synthase-1 deletion leads to adverse left ventricular remodeling after myocardial infarction. Circulation 117:1701–1710. [CrossRef]
76. Qian JY, Harding P, Liu Y, Shesely E, Yang XP, LaPointe MC. 2008. Reduced cardiac remodeling and function in cardiac-specific EP4 receptor knockout mice with myocardial infarction. Hypertension 51:560–566. [CrossRef]
77. Bunting S, Moncada S, Vane JR. 1983. The prostacyclin-thromboxane A2 balance: pathophysiological and therapeutic implications. Br Med Bull 39:271–276.
78. FitzGerald GA. 2003. COX-2 and beyond: approaches to prostaglandin inhibition in human disease. Nat Rev Drug Discov 2:879–890. [CrossRef]
79. de Nucci G, Gryglewski RJ, Warner TD, Vane JR. 1988. Receptor-mediated release of endothelium-derived relaxing factor and prostacyclin from bovine aortic endothelial cells is coupled. Proc Natl Acad Sci U S A 85:2334–2338. [CrossRef]
80. Palmer RM, Ferrige AG, Moncada S. 1987. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 327:524–526. [CrossRef]
81. Ellis EF, Oelz O, Roberts LJ II, Payne NA, Sweetman BJ, Nies AS, Oates JA. 1976. Coronary arterial smooth muscle contraction by a substance released from platelets: evidence that it is thromboxane A2. Science 193:1135–1137. [CrossRef]
82. Hamberg M, Svensson J, Samuelsson B. 1975. Thromboxanes: a new group of biologically active compounds derived from prostaglandin endoperoxides. Proc Natl Acad Sci U S A 72:2994–2998. [CrossRef]
83. Salzman PM, Salmon JA, Moncada S. 1980. Prostacyclin and thromboxane A2 synthesis by rabbit pulmonary artery. J Pharmacol Exp Ther 215:240–247.
84. Rocca B, Secchiero P, Ciabattoni G, Ranelletti FO, Catani L, Guidotti L, Melloni E, Maggiano N, Zauli G, Patrono C. 2002. Cyclooxygenase-2 expression is induced during human megakaryopoiesis and characterizes newly formed platelets. Proc Natl Acad Sci U S A 99:7634–7639. [CrossRef]
85. Aronoff DM, Carstens JK, Chen GH, Toews GB, Peters-Golden M. 2006. Short communication: differences between macrophages and dendritic cells in the cyclic AMP-dependent regulation of lipopolysaccharide-induced cytokine and chemokine synthesis. J Interferon Cytokine Res 26:827–833. [CrossRef]
86. Luo M, Jones SM, Phare SM, Coffey MJ, Peters-Golden M, Brock TG. 2004. Protein kinase A inhibits leukotriene synthesis by phosphorylation of 5-lipoxygenase on serine 523. J Biol Chem 279:41512–41520. [CrossRef]
87. van der Pouw Kraan TC, van Lier RA, Aarden LA. 1995. PGE2 and the immune response. A central role for prostaglandin E2 in downregulating the inflammatory immune response. Mol Med Today 1:61. [CrossRef]
88. Aronoff DM, Canetti C, Peters-Golden M. 2004. Prostaglandin E2 inhibits alveolar macrophage phagocytosis through an E-prostanoid 2 receptor-mediated increase in intracellular cyclic AMP. J Immunol 173:559–565. [CrossRef]
89. Rossi AG, McCutcheon JC, Roy N, Chilvers ER, Haslett C, Dransfield I. 1998. Regulation of macrophage phagocytosis of apoptotic cells by cAMP. J Immunol 160:3562–3568.
90. Serezani CH, Chung J, Ballinger MN, Moore BB, Aronoff DM, Peters-Golden M. 2007. Prostaglandin E2 suppresses bacterial killing in alveolar macrophages by inhibiting NADPH oxidase. Am J Respir Cell Mol Biol 37:562–570. [CrossRef]
91. Soares AC, Souza DG, Pinho V, Vieira AT, Barsante MM, Nicoli JR, Teixeira M. 2003. Impaired host defense to Klebsiella pneumoniae infection in mice treated with the PDE4 inhibitor rolipram. Br J Pharmacol 140:855–862. [CrossRef]
92. Weinberg DA, Weston LK, Kaplan JE. 1985. Influence of prostaglandin I2 on fibronectin-mediated phagocytosis in vivo and in vitro. J Leukoc Biol 37:151–159.
93. Ydrenius L, Majeed M, Rasmusson BJ, Stendahl O, Särndahl E. 2000. Activation of cAMP-dependent protein kinase is necessary for actin rearrangements in human neutrophils during phagocytosis. J Leukoc Biol 67:520–528.
94. Aronoff DM, Peres CM, Serezani CH, Ballinger MN, Carstens JK, Coleman N, Moore BB, Peebles RS, Faccioli LH, Peters-Golden M. 2007. Synthetic prostacyclin analogs differentially regulate macrophage function via distinct analog-receptor binding specificities. J Immunol 178:1628–1634. [CrossRef]
95. Brandwein SR. 1986. Regulation of interleukin 1 production by mouse peritoneal macrophages. Effects of arachidonic acid metabolites, cyclic nucleotides, and interferons. J Biol Chem 261:8624–8632.
96. Kunkel SL, Spengler M, May MA, Spengler R, Larrick J, Remick D. 1988. Prostaglandin E2 regulates macrophage-derived tumor necrosis factor gene expression. J Biol Chem 263:5380–5384.
97. Kunkel SL, Wiggins RC, Chensue SW, Larrick J. 1986. Regulation of macrophage tumor necrosis factor production by prostaglandin E2. Biochem Biophys Res Commun 137:404–410. [CrossRef]
98. Takayama K, García-Cardena G, Sukhova GK, Comander J, Gimbrone MA, Jr, Libby P. 2002. Prostaglandin E2 suppresses chemokine production in human macrophages through the EP4 receptor. J Biol Chem 277:44147–44154. [CrossRef]
99. van der Pouw Kraan TC, Boeije LC, Snijders A, Smeenk RJ, Wijdenes J, Aarden LA. 1996. Regulation of IL-12 production by human monocytes and the influence of prostaglandin E2. Ann N Y Acad Sci 795:147–157. [CrossRef]
100. Xu XJ, Reichner JS, Mastrofrancesco B, Henry WL, Jr, Albina JE. 2008. Prostaglandin E2 suppresses lipopolysaccharide-stimulated IFN-β production. J Immunol 180:2125–2131. [CrossRef]
101. Harizi H, Juzan M, Pitard V, Moreau JF, Gualde N. 2002. Cyclooxygenase-2-issued prostaglandin E2 enhances the production of endogenous IL-10, which down-regulates dendritic cell functions. J Immunol 168:2255–2263. [CrossRef]
102. Hinson RM, Williams JA, Shacter E. 1996. Elevated interleukin 6 is induced by prostaglandin E2 in a murine model of inflammation: possible role of cyclooxygenase-2. Proc Natl Acad Sci U S A 93:4885–4890. [CrossRef]
103. Starczewski M, Voigtmann R, Peskar BA, Peskar BM. 1984. Plasma levels of 15-keto-13,14-dihydro-prostaglandin E2 in patients with bronchogenic carcinoma. Prostaglandins Leukot Med 13:249–258. [CrossRef]
104. Hayek MG, Mura C, Wu D, Beharka AA, Han SN, Paulson KE, Hwang D, Meydani SN. 1997. Enhanced expression of inducible cyclooxygenase with age in murine macrophages. J Immunol 159:2445–2451.
105. Medjane S, Raymond B, Wu Y, Touqui L. 2005. Impact of CFTR ΔF508 mutation on prostaglandin E2 production and type IIA phospholipase A2 expression by pulmonary epithelial cells. Am J Physiol Lung Cell Mol Physiol 289:L816–L824. [CrossRef]
106. Strandvik B, Svensson E, Seyberth HW. 1996. Prostanoid biosynthesis in patients with cystic fibrosis. Prostaglandins Leukot Essent Fatty Acids 55:419–425. [CrossRef]
107. Levy BD, Clish CB, Schmidt B, Gronert K, Serhan CN. 2001. Lipid mediator class switching during acute inflammation: signals in resolution. Nat Immunol 2:612–619. [CrossRef]
108. Hong S, Gronert K, Devchand PR, Moussignac RL, Serhan CN. 2003. Novel docosatrienes and 17S-resolvins generated from docosahexaenoic acid in murine brain, human blood, and glial cells. Autacoids in anti-inflammation. J Biol Chem 278:14677–14687. [CrossRef]
109. Marcheselli VL, Hong S, Lukiw WJ, Tian XH, Gronert K, Musto A, Hardy M, Gimenez JM, Chiang N, Serhan CN, Bazan NG. 2003. Novel docosanoids inhibit brain ischemia-reperfusion-mediated leukocyte infiltration and pro-inflammatory gene expression. J Biol Chem 278:43807–43817. [CrossRef]
110. Serhan CN, Clish CB, Brannon J, Colgan SP, Chiang N, Gronert K. 2000. Novel functional sets of lipid-derived mediators with antiinflammatory actions generated from omega-3 fatty acids via cyclooxygenase 2-nonsteroidal antiinflammatory drugs and transcellular processing. J Exp Med 192:1197–1204. [CrossRef]
111. Serhan CN, Hong S, Gronert K, Colgan SP, Devchand PR, Mirick G, Moussignac RL. 2002. Resolvins: a family of bioactive products of omega-3 fatty acid transformation circuits initiated by aspirin treatment that counter proinflammation signals. J Exp Med 196:1025–1037. [CrossRef]
112. Clark RB, Bishop-Bailey D, Estrada-Hernandez T, Hla T, Puddington L, Padula SJ. 2000. The nuclear receptor PPARγ and immunoregulation: PPARγ mediates inhibition of helper T cell responses. J Immunol 164:1364–1371. [CrossRef]
113. Combs CK, Johnson DE, Karlo JC, Cannady SB, Landreth GE. 2000. Inflammatory mechanisms in Alzheimer’s disease: inhibition of β-amyloid-stimulated proinflammatory responses and neurotoxicity by PPARγ agonists. J Neurosci 20:558–567.
114. Diab A, Deng C, Smith JD, Hussain RZ, Phanavanh B, Lovett-Racke AE, Drew PD, Racke MK. 2002. Peroxisome proliferator-activated receptor-γ agonist 15-deoxy-Δ12,14-prostaglandin J2 ameliorates experimental autoimmune encephalomyelitis. J Immunol 168:2508–2515. [CrossRef]
115. Kawahito Y, Kondo M, Tsubouchi Y, Hashiramoto A, Bishop-Bailey D, Inoue K, Kohno M, Yamada R, Hla T, Sano H. 2000. 15-Deoxy-Δ12,14-PGJ2 induces synoviocyte apoptosis and suppresses adjuvant-induced arthritis in rats. J Clin Invest 106:189–197. [CrossRef]
116. Reilly CM, Oates JC, Cook JA, Morrow JD, Halushka PV, Gilkeson GS. 2000. Inhibition of mesangial cell nitric oxide in MRL/lpr mice by prostaglandin J2 and proliferator activation receptor-γ agonists. J Immunol 164:1498–1504. [CrossRef]
117. Kim EH, Na HK, Surh YJ. 2006. Upregulation of VEGF by 15-deoxy-Δ12,14-prostaglandin J2 via heme oxygenase-1 and ERK1/2 signaling in MCF-7 cells. Ann N Y Acad Sci 1090:375–384. [CrossRef]
118. Oliva JL, Pérez-Sala D, Castrillo A, Martínez N, Cañada FJ, Boscá L, Rojas JM. 2003. The cyclopentenone 15-deoxy-Δ12,14-prostaglandin J2 binds to and activates H-Ras. Proc Natl Acad Sci USA 100:4772–4777. [CrossRef]
119. Renedo M, Gayarre J, García-Domínguez CA, Pérez-Rodríguez A, Prieto A, Cañada FJ, Rojas JM, Pérez-Sala D. 2007. Modification and activation of Ras proteins by electrophilic prostanoids with different structure are site-selective. Biochemistry 46:6607–6616. [CrossRef]
120. Khan MM. 1995. Regulation of IL-4 and IL-5 secretion by histamine and PGE2. Adv Exp Med Biol 383:35–42. [CrossRef]
121. Jiang C, Ting AT, Seed B. 1998. PPAR-γ agonists inhibit production of monocyte inflammatory cytokines. Nature 391:82–86. [CrossRef]
122. Ricote M, Li AC, Willson TM, Kelly CJ, Glass CK. 1998. The peroxisome proliferator-activated receptor-γ is a negative regulator of macrophage activation. Nature 391:79–82. [CrossRef]
123. Cernuda-Morollón E, Pineda-Molina E, Cañada FJ, Pérez-Sala D. 2001. 15-Deoxy-Δ12,14-prostaglandin J2 inhibition of NF-κB-DNA binding through covalent modification of the p50 subunit. J Biol Chem 276:35530–35536. [CrossRef]
124. Rossi A, Kapahi P, Natoli G, Takahashi T, Chen Y, Karin M, Santoro MG. 2000. Anti-inflammatory cyclopentenone prostaglandins are direct inhibitors of IκB kinase. Nature 403:103–108. [CrossRef]
125. Straus DS, Pascual G, Li M, Welch JS, Ricote M, Hsiang CH, Sengchanthalangsy LL, Ghosh G, Glass CK. 2000. 15-Deoxy-Δ12,14-prostaglandin J2 inhibits multiple steps in the NF-κB signaling pathway. Proc Natl Acad Sci U S A 97:4844–4849. [CrossRef]
126. Jackson SM, Parhami F, Xi XP, Berliner JA, Hsueh WA, Law RE, Demer LL. 1999. Peroxisome proliferator-activated receptor activators target human endothelial cells to inhibit leukocyte-endothelial cell interaction. Arterioscler Thromb Vasc Biol 19:2094–2104. [CrossRef]
127. Pasceri V, Wu HD, Willerson JT, Yeh ET. 2000. Modulation of vascular inflammation in vitro and in vivo by peroxisome proliferator-activated receptor-γ activators. Circulation 101:235–238. [CrossRef]
128. Zhang X, Wang JM, Gong WH, Mukaida N, Young HA. 2001. Differential regulation of chemokine gene expression by 15-deoxy-Δ12,14 prostaglandin J2. J Immunol 166:7104–7111. [CrossRef]
129. Lawrence T. 2002. Modulation of inflammation in vivo through induction of the heat shock response, effects on NF-κB activation. Inflamm Res 51:108–109. [CrossRef]
130. Bishop-Bailey D, Hla T. 1999. Endothelial cell apoptosis induced by the peroxisome proliferator-activated receptor (PPAR) ligand 15-deoxy-Δ12,14-prostaglandin J2. J Biol Chem 274:17042–17048. [CrossRef]
131. Khoshnan A, Tindell C, Laux I, Bae D, Bennett B, Nel AE. 2000. The NF-κB cascade is important in Bcl-xL expression and for the anti-apoptotic effects of the CD28 receptor in primary human CD4+ lymphocytes. J Immunol 165:1743–1754. [CrossRef]
132. Lawrence T, Gilroy DW, Colville-Nash PR, Willoughby DA. 2001. Possible new role for NF-κB in the resolution of inflammation. Nat Med 7:1291–1297. [CrossRef]
133. Ward C, Dransfield I, Murray J, Farrow SN, Haslett C, Rossi AG. 2002. Prostaglandin D2 and its metabolites induce caspase-dependent granulocyte apoptosis that is mediated via inhibition of IκBα degradation using a peroxisome proliferator-activated receptor-γ-independent mechanism. J Immunol 168:6232–6243. [CrossRef]
134. Trivedi SG, Newson J, Rajakariar R, Jacques TS, Hannon R, Kanaoka Y, Eguchi N, Colville-Nash P, Gilroy DW. 2006. Essential role for hematopoietic prostaglandin D2 synthase in the control of delayed type hypersensitivity. Proc Natl Acad Sci U S A 103:5179–5184. [CrossRef]
135. Lewis RA, Austen KF, Drazen JM, Clark DA, Marfat A, Corey EJ. 1980. Slow reacting substances of anaphylaxis: identification of leukotrienes C-1 and D from human and rat sources. Proc Natl Acad Sci U S A 77:3710–3714. [CrossRef]
136. Borgeat P, Samuelsson B. 1979. Arachidonic acid metabolism in polymorphonuclear leukocytes: effects of ionophore A23187. Proc Natl Acad Sci U S A 76:2148–2152. [CrossRef]
137. Smith MJ. 1979. Prostaglandins and the polymorphonuclear leucocyte. Agents Actions Suppl 1979(6):91–103. [CrossRef]
138. Funk CD. 2001. Prostaglandins and leukotrienes: advances in eicosanoid biology. Science 294:1871–1875. [CrossRef]
139. Minami M, Ohno S, Kawasaki H, Rådmark O, Samuelsson B, Jörnvall H, Shimizu T, Seyama Y, Suzuki K. 1987. Molecular cloning of a cDNA coding for human leukotriene A4 hydrolase. Complete primary structure of an enzyme involved in eicosanoid synthesis. J Biol Chem 262:13873–13876.
140. Hammarström S, Orning L, Bernström K. 1985. Metabolism of leukotrienes. Mol Cell Biochem 69:7–16. [CrossRef]
141. Lam BK, Gagnon L, Austen KF, Soberman RJ. 1990. The mechanism of leukotriene B4 export from human polymorphonuclear leukocytes. J Biol Chem 265:13438–13441.
142. Leier I, Jedlitschky G, Buchholz U, Keppler D. 1994. Characterization of the ATP-dependent leukotriene C4 export carrier in mastocytoma cells. Eur J Biochem 220:599–606. [CrossRef]
143. Rouzer CA, Samuelsson B. 1985. On the nature of the 5-lipoxygenase reaction in human leukocytes: enzyme purification and requirement for multiple stimulatory factors. Proc Natl Acad Sci U S A 82:6040–6044. [CrossRef]
144. Ochi K, Yoshimoto T, Yamamoto S, Taniguchi K, Miyamoto T. 1983. Arachidonate 5-lipoxygenase of guinea pig peritoneal polymorphonuclear leukocytes. Activation by adenosine 5′-triphosphate. J Biol Chem 258:5754–5758.
145. Werz O, Szellas D, Steinhilber D, Rådmark O. 2002. Arachidonic acid promotes phosphorylation of 5-lipoxygenase at Ser-271 by MAPK-activated protein kinase 2 (MK2). J Biol Chem 277:14793–14800. [CrossRef]
146. Kanaoka Y, Boyce JA. 2004. Cysteinyl leukotrienes and their receptors: cellular distribution and function in immune and inflammatory responses. J Immunol 173:1503–1510. [CrossRef]
147. Tager AM, Luster AD. 2003. BLT1 and BLT2: the leukotriene B4 receptors. Prostaglandins Leukot Essent Fatty Acids 69:123–134. [CrossRef]
148. Lynch KR, O’Neill GP, Liu Q, Im DS, Sawyer N, Metters KM, Coulombe N, Abramovitz M, Figueroa DJ, Zeng Z, Connolly BM, Bai C, Austin CP, Chateauneuf A, Stocco R, Greig GM, Kargman S, Hooks SB, Hosfield E, Williams DL, Jr, Ford-Hutchinson AW, Caskey CT, Evans JF. 1999. Characterization of the human cysteinyl leukotriene CysLT1 receptor. Nature 399:789–793. [CrossRef]
149. Beller TC, Friend DS, Maekawa A, Lam BK, Austen KF, Kanaoka Y. 2004. Cysteinyl leukotriene 1 receptor controls the severity of chronic pulmonary inflammation and fibrosis. Proc Natl Acad Sci U S A 101:3047–3052. [CrossRef]
150. Hui Y, Cheng Y, Smalera I, Jian W, Goldhahn L, Fitzgerald GA, Funk CD. 2004. Directed vascular expression of human cysteinyl leukotriene 2 receptor modulates endothelial permeability and systemic blood pressure. Circulation 110:3360–3366. [CrossRef]
151. Sousa AR, Parikh A, Scadding G, Corrigan CJ, Lee TH. 2002. Leukotriene-receptor expression on nasal mucosal inflammatory cells in aspirin-sensitive rhinosinusitis. N Engl J Med 347:1493–1499. [CrossRef]
152. Devchand PR, Keller H, Peters JM, Vazquez M, Gonzalez FJ, Wahli W. 1996. The PPARα-leukotriene B4 pathway to inflammation control. Nature 384:39–43. [CrossRef]
153. Krey G, Braissant O, L’Horset F, Kalkhoven E, Perroud M, Parker MG, Wahli W. 1997. Fatty acids, eicosanoids, and hypolipidemic agents identified as ligands of peroxisome proliferator-activated receptors by coactivator-dependent receptor ligand assay. Mol Endocrinol 11:779–791. [CrossRef]
154. Lin Q, Ruuska SE, Shaw NS, Dong D, Noy N. 1999. Ligand selectivity of the peroxisome proliferator-activated receptor α. Biochemistry 38:185–190. [CrossRef]
155. Narala VR, Adapala RK, Suresh MV, Brock TG, Peters-Golden M, Reddy RC. 2010. Leukotriene B4 is a physiologically relevant endogenous peroxisome proliferator-activated receptor-α agonist. J Biol Chem 285:22067–22074. [CrossRef]
156. Borgeat P, Naccache PH. 1990. Biosynthesis and biological activity of leukotriene B4. Clin Biochem 23:459–468. [CrossRef]
157. Ott VL, Cambier JC, Kappler J, Marrack P, Swanson BJ. 2003. Mast cell-dependent migration of effector CD8+ T cells through production of leukotriene B4. Nat Immunol 4:974–981. [CrossRef]
158. Woodward DF, Krauss AH, Nieves AL, Spada CS. 1991. Studies on leukotriene D4 as an eosinophil chemoattractant. Drugs Exp Clin Res 17:543–548.
159. Björk J, Hedqvist P, Arfors KE. 1982. Increase in vascular permeability induced by leukotriene B4 and the role of polymorphonuclear leukocytes. Inflammation 6:189–200. [CrossRef]
160. Dahlén SE, Björk J, Hedqvist P, Arfors KE, Hammarström S, Lindgren JA, Samuelsson B. 1981. Leukotrienes promote plasma leakage and leukocyte adhesion in postcapillary venules: in vivo effects with relevance to the acute inflammatory response. Proc Natl Acad Sci U S A 78:3887–3891. [CrossRef]
161. Hedqvist P, Dahlén SE. 1983. Pulmonary and vascular effects of leukotrienes imply involvement in asthma and inflammation. Adv Prostaglandin Thromboxane Leukot Res 11:27–32.
162. Orange RP, Stechschulte DJ, Austen KF. 1969. Cellular mechanisms involved in the release of slow reacting substance of anaphylaxis. Fed Proc 28:1710–1715.
163. Svensjö E. 1978. Bradykinin and prostaglandin E1, E2 and F-induced macromolecular leakage in the hamster cheek pouch. Prostaglandins Med 1:397–410. [CrossRef]
164. Werz O, Steinhilber D. 2005. Development of 5-lipoxygenase inhibitors—lessons from cellular enzyme regulation. Biochem Pharmacol 70:327–333. [CrossRef]
165. Israel E, Rubin P, Kemp JP, Grossman J, Pierson W, Siegel SC, Tinkelman D, Murray JJ, Busse W, Segal AT, Fish J, Kaiser HB, Ledford D, Wenzel S, Rosenthal R, Cohn J, Lanni C, Pearlman H, Karahalios P, Drazen JM. 1993. The effect of inhibition of 5-lipoxygenase by zileuton in mild-to-moderate asthma. Ann Intern Med 119:1059–1066. [CrossRef]
166. Knorr B, Matz J, Bernstein JA, Nguyen H, Seidenberg BC, Reiss TF, Becker A, Pediatric Montelukast Study Group. 1998. Montelukast for chronic asthma in 6- to 14-year-old children: a randomized, double-blind trial. JAMA 279:1181–1186. [CrossRef]
167. Suissa S, Dennis R, Ernst P, Sheehy O, Wood-Dauphinee S. 1997. Effectiveness of the leukotriene receptor antagonist zafirlukast for mild-to-moderate asthma. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 126:177–183. [CrossRef]
168. Spanbroek R, Grabner R, Lotzer K, Hildner M, Urbach A, Ruhling K, Moos MP, Kaiser B, Cohnert TU, Wahlers T, Zieske A, Plenz G, Robenek H, Salbach P, Kuhn H, Radmark O, Samuelsson B, Habenicht AJ. 2003. Expanding expression of the 5-lipoxygenase pathway within the arterial wall during human atherogenesis. Proc Natl Acad Sci U S A 100:1238–1243. [CrossRef]
169. Qiu H, Gabrielsen A, Agardh HE, Wan M, Wetterholm A, Wong CH, Hedin U, Swedenborg J, Hansson GK, Samuelsson B, Paulsson-Berne G, Haeggström JZ. 2006. Expression of 5-lipoxygenase and leukotriene A4 hydrolase in human atherosclerotic lesions correlates with symptoms of plaque instability. Proc Natl Acad Sci U S A 103:8161–8166. [CrossRef]
170. Aiello RJ, Bourassa PA, Lindsey S, Weng W, Freeman A, Showell HJ. 2002. Leukotriene B4 receptor antagonism reduces monocytic foam cells in mice. Arterioscler Thromb Vasc Biol 22:443–449. [CrossRef]
171. Bäck M, Bu DX, Bränström R, Sheikine Y, Yan ZQ, Hansson GK. 2005. Leukotriene B4 signaling through NF-κB-dependent BLT1 receptors on vascular smooth muscle cells in atherosclerosis and intimal hyperplasia. Proc Natl Acad Sci U S A 102:17501–17506. [CrossRef]
172. Uzonyi B, Lötzer K, Jahn S, Kramer C, Hildner M, Bretschneider E, Radke D, Beer M, Vollandt R, Evans JF, Funk CD, Habenicht AJ. 2006. Cysteinyl leukotriene 2 receptor and protease-activated receptor 1 activate strongly correlated early genes in human endothelial cells. Proc Natl Acad Sci U S A 103:6326–6331. [CrossRef]
173. Zhao L, Moos MP, Gräbner R, Pédrono F, Fan J, Kaiser B, John N, Schmidt S, Spanbroek R, Lötzer K, Huang L, Cui J, Rader DJ, Evans JF, Habenicht AJ, Funk CD. 2004. The 5-lipoxygenase pathway promotes pathogenesis of hyperlipidemia-dependent aortic aneurysm. Nat Med 10:966–973. [CrossRef]
174. Helgadottir A, Manolescu A, Helgason A, Thorleifsson G, Thorsteinsdottir U, Gudbjartsson DF, Gretarsdottir S, Magnusson KP, Gudmundsson G, Hicks A, Jonsson T, Grant SF, Sainz J, O’Brien SJ, Sveinbjornsdottir S, Valdimarsson EM, Matthiasson SE, Levey AI, Abramson JL, Reilly MP, Vaccarino V, Wolfe ML, Gudnason V, Quyyumi AA, Topol EJ, Rader DJ, Thorgeirsson G, Gulcher JR, Hakonarson H, Kong A, Stefansson K. 2006. A variant of the gene encoding leukotriene A4 hydrolase confers ethnicity-specific risk of myocardial infarction. Nat Genet 38:68–74. [CrossRef]
175. Helgadottir A, Manolescu A, Thorleifsson G, Gretarsdottir S, Jonsdottir H, Thorsteinsdottir U, Samani NJ, Gudmundsson G, Grant SF, Thorgeirsson G, Sveinbjornsdottir S, Valdimarsson EM, Matthiasson SE, Johannsson H, Gudmundsdottir O, Gurney ME, Sainz J, Thorhallsdottir M, Andresdottir M, Frigge ML, Topol EJ, Kong A, Gudnason V, Hakonarson H, Gulcher JR, Stefansson K. 2004. The gene encoding 5-lipoxygenase activating protein confers risk of myocardial infarction and stroke. Nat Genet 36:233–239. [CrossRef]
176. Kajimoto K, Shioji K, Ishida C, Iwanaga Y, Kokubo Y, Tomoike H, Miyazaki S, Nonogi H, Goto Y, Iwai N. 2005. Validation of the association between the gene encoding 5-lipoxygenase-activating protein and myocardial infarction in a Japanese population. Circ J 69:1029–1034. [CrossRef]
177. Hakonarson H, Thorvaldsson S, Helgadottir A, Gudbjartsson D, Zink F, Andresdottir M, Manolescu A, Arnar DO, Andersen K, Sigurdsson A, Thorgeirsson G, Jonsson A, Agnarsson U, Bjornsdottir H, Gottskalksson G, Einarsson A, Gudmundsdottir H, Adalsteinsdottir AE, Gudmundsson K, Kristjansson K, Hardarson T, Kristinsson A, Topol EJ, Gulcher J, Kong A, Gurney M, Thorgeirsson G, Stefansson K. 2005. Effects of a 5-lipoxygenase-activating protein inhibitor on biomarkers associated with risk of myocardial infarction: a randomized trial. JAMA 293:2245–2256. [CrossRef]
178. Peters-Golden M, Canetti C, Mancuso P, Coffey MJ. 2005. Leukotrienes: underappreciated mediators of innate immune responses. J Immunol 174:589–594. [CrossRef]
179. Bailie MB, Standiford TJ, Laichalk LL, Coffey MJ, Strieter R, Peters-Golden M. 1996. Leukotriene-deficient mice manifest enhanced lethality from Klebsiella pneumonia in association with decreased alveolar macrophage phagocytic and bactericidal activities. J Immunol 157:5221–5224.
180. Mancuso P, Lewis C, Serezani CH, Goel D, Peters-Golden M. 2010. Intrapulmonary administration of leukotriene B4 enhances pulmonary host defense against pneumococcal pneumonia. Infect Immun 78:2264–2271. [CrossRef]
181. Medeiros AI, Sá-Nunes A, Turato WM, Secatto A, Frantz FG, Sorgi CA, Serezani CH, Deepe GS, Jr, Faccioli LH. 2008. Leukotrienes are potent adjuvant during fungal infection: effects on memory T cells. J Immunol 181:8544–8551. [CrossRef]
182. Peres CM, de Paula L, Medeiros AI, Sorgi CA, Soares EG, Carlos D, Peters-Golden M, Silva CL, Faccioli LH. 2007. Inhibition of leukotriene biosynthesis abrogates the host control of Mycobacterium tuberculosis. Microbes Infect 9:483–489. [CrossRef]
183. Schultz MJ, Wijnholds J, Peppelenbosch MP, Vervoordeldonk MJ, Speelman P, van Deventer SJ, Borst P, van der Poll T. 2001. Mice lacking the multidrug resistance protein 1 are resistant to Streptococcus pneumoniae-induced pneumonia. J Immunol 166:4059–4064. [CrossRef]
184. Serezani CH, Perrela JH, Russo M, Peters-Golden M, Jancar S. 2006. Leukotrienes are essential for the control of Leishmania amazonensis infection and contribute to strain variation in susceptibility. J Immunol 177:3201–3208. [CrossRef]
185. Serezani CH, Aronoff DM, Jancar S, Mancuso P, Peters-Golden M. 2005. Leukotrienes enhance the bactericidal activity of alveolar macrophages against Klebsiella pneumoniae through the activation of NADPH oxidase. Blood 106:1067–1075. [CrossRef]
186. Ballinger MN, Hubbard LL, McMillan TR, Toews GB, Peters-Golden M, Paine R, III, Moore BB. 2008. Paradoxical role of alveolar macrophage-derived granulocyte-macrophage colony-stimulating factor in pulmonary host defense post-bone marrow transplantation. Am J Physiol Lung Cell Mol Physiol 295:L114–L122. [CrossRef]
187. Balter MS, Toews GB, Peters-Golden M. 1989. Multiple defects in arachidonate metabolism in alveolar macrophages from young asymptomatic smokers. J Lab Clin Med 114:662–673.
188. Cederholm T, Lindgren JA, Palmblad J. 2000. Impaired leukotriene C4 generation in granulocytes from protein-energy malnourished chronically ill elderly. J Intern Med 247:715–722. [CrossRef]
189. Coffey MJ, Phare SM, Kazanjian PH, Peters-Golden M. 1996. 5-Lipoxygenase metabolism in alveolar macrophages from subjects infected with the human immunodeficiency virus. J Immunol 157:393–399.
190. Coffey MJ, Wilcoxen SE, Phare SM, Simpson RU, Gyetko MR, Peters-Golden M. 1994. Reduced 5-lipoxygenase metabolism of arachidonic acid in macrophages from 1,25-dihydroxyvitamin D3-deficient rats. Prostaglandins 48:313–329. [CrossRef]
191. Jubiz W, Draper RE, Gale J, Nolan G. 1984. Decreased leukotriene B4 synthesis by polymorphonuclear leukocytes from male patients with diabetes mellitus. Prostaglandins Leukot Med 14:305–311. [CrossRef]
192. Lärfars G, Lantoine F, Devynck MA, Palmblad J, Gyllenhammar H. 1999. Activation of nitric oxide release and oxidative metabolism by leukotrienes B4, C4, and D4 in human polymorphonuclear leukocytes. Blood 93:1399–1405.
193. Talvani A, Machado FS, Santana GC, Klein A, Barcelos L, Silva JS, Teixeira MM. 2002. Leukotriene B4 induces nitric oxide synthesis in Trypanosoma cruzi-infected murine macrophages and mediates resistance to infection. Infect Immun 70:4247–4253. [CrossRef]
194. Flamand L, Tremblay MJ, Borgeat P. 2007. Leukotriene B4 triggers the in vitro and in vivo release of potent antimicrobial agents. J Immunol 178:8036–8045. [CrossRef]
195. Powell WS, Gravelle F, Gravel S. 1992. Metabolism of 5(S)-hydroxy-6,8,11,14-eicosatetraenoic acid and other 5(S)-hydroxyeicosanoids by a specific dehydrogenase in human polymorphonuclear leukocytes. J Biol Chem 267:19233–19241.
196. Graham FD, Erlemann KR, Gravel S, Rokach J, Powell WS. 2009. Oxidative stress-induced changes in pyridine nucleotides and chemoattractant 5-lipoxygenase products in aging neutrophils. Free Radic Biol Med 47:62–71. [CrossRef]
197. Powell WS, Gravelle F, Gravel S. 1994. Phorbol myristate acetate stimulates the formation of 5-oxo-6,8,11,14-eicosatetraenoic acid by human neutrophils by activating NADPH oxidase. J Biol Chem 269:25373–25380.
198. Cossette C, Patel P, Anumolu JR, Sivendran S, Lee GJ, Gravel S, Graham FD, Lesimple A, Mamer OA, Rokach J, Powell WS. 2008. Human neutrophils convert the sebum-derived polyunsaturated fatty acid sebaleic acid to a potent granulocyte chemoattractant. J Biol Chem 283:11234–11243. [CrossRef]
199. Patel P, Cossette C, Anumolu JR, Gravel S, Lesimple A, Mamer OA, Rokach J, Powell WS. 2008. Structural requirements for activation of the 5-oxo-6E,8Z, 11Z,14Z-eicosatetraenoic acid (5-oxo-ETE) receptor: identification of a mead acid metabolite with potent agonist activity. J Pharmacol Exp Ther 325:698–707. [CrossRef]
200. Powell WS, Chung D, Gravel S. 1995. 5-Oxo-6,8,11,14-eicosatetraenoic acid is a potent stimulator of human eosinophil migration. J Immunol 154:4123–4132.
201. Powell WS, Rokach J. 2005. Biochemistry, biology and chemistry of the 5-lipoxygenase product 5-oxo-ETE. Prog Lipid Res 44:154–183. [CrossRef]
202. Brink CB, Harvey BH, Bodenstein J, Venter DP, Oliver DW. 2004. Recent advances in drug action and therapeutics: relevance of novel concepts in G-protein-coupled receptor and signal transduction pharmacology. Br J Clin Pharmacol 57:373–387. [CrossRef]
203. Takeda S, Kadowaki S, Haga T, Takaesu H, Mitaku S. 2002. Identification of G protein-coupled receptor genes from the human genome sequence. FEBS Lett 520:97–101. [CrossRef]
204. Hosoi T, Koguchi Y, Sugikawa E, Chikada A, Ogawa K, Tsuda N, Suto N, Tsunoda S, Taniguchi T, Ohnuki T. 2002. Identification of a novel human eicosanoid receptor coupled to Gi/o. J Biol Chem 277:31459–31465. [CrossRef]
205. Jones CE, Holden S, Tenaillon L, Bhatia U, Seuwen K, Tranter P, Turner J, Kettle R, Bouhelal R, Charlton S, Nirmala NR, Jarai G, Finan P. 2003. Expression and characterization of a 5-oxo-6E,8Z,11Z,14Z-eicosatetraenoic acid receptor highly expressed on human eosinophils and neutrophils. Mol Pharmacol 63:471–477. [CrossRef]
206. Norgauer J, Barbisch M, Czech W, Pareigis J, Schwenk U, Schröder JM. 1996. Chemotactic 5-oxo-icosatetraenoic acids activate a unique pattern of neutrophil responses. Analysis of phospholipid metabolism, intracellular Ca2+ transients, actin reorganization, superoxide-anion production and receptor up-regulation. Eur J Biochem 236:1003–1009. [CrossRef]
207. O’Flaherty JT, Kuroki M, Nixon AB, Wijkander J, Yee E, Lee SL, Smitherman PK, Wykle RL, Daniel LW. 1996. 5-Oxo-eicosanoids and hematopoietic cytokines cooperate in stimulating neutrophil function and the mitogen-activated protein kinase pathway. J Biol Chem 271:17821–17828. [CrossRef]
208. Hosoi T, Sugikawa E, Chikada A, Koguchi Y, Ohnuki T. 2005. TG1019/OXE, a Gαi/o-protein-coupled receptor, mediates 5-oxo-eicosatetraenoic acid-induced chemotaxis. Biochem Biophys Res Commun 334:987–995. [CrossRef]
209. O’Flaherty JT, Rogers LC, Chadwell BA, Owen JS, Rao A, Cramer SD, Daniel LW. 2002. 5(S)-Hydroxy-6,8,11,14-E,Z,Z,Z-eicosatetraenoate stimulates PC3 cell signaling and growth by a receptor-dependent mechanism. Cancer Res 62:6817–6819.
210. Langlois A, Chouinard F, Flamand N, Ferland C, Rola-Pleszczynski M, Laviolette M. 2009. Crucial implication of protein kinase C (PKC)-δ, PKC-ζ, ERK-1/2, and p38 MAPK in migration of human asthmatic eosinophils. J Leukoc Biol 85:656–663. [CrossRef]
211. O’Flaherty JT, Kuroki M, Nixon AB, Wijkander J, Yee E, Lee SL, Smitherman PK, Wykle RL, Daniel LW. 1996. 5-Oxo-eicosatetraenoate is a broadly active, eosinophil-selective stimulus for human granulocytes. J Immunol 157:336–342.
212. Stamatiou PB, Chan CC, Monneret G, Ethier D, Rokach J, Powell WS. 2004. 5-Oxo-6,8,11,14-eicosatetraenoic acid stimulates the release of the eosinophil survival factor granulocyte/macrophage colony-stimulating factor from monocytes. J Biol Chem 279:28159–28164. [CrossRef]
213. Ghosh S, Karin M. 2002. Missing pieces in the NF-κB puzzle. Cell 109(Suppl):S81–S96. [CrossRef]
214. Sundaram S, Ghosh J. 2006. Expression of 5-oxoETE receptor in prostate cancer cells: critical role in survival. Biochem Biophys Res Commun 339:93–98. [CrossRef]
215. Clària J, Serhan CN. 1995. Aspirin triggers previously undescribed bioactive eicosanoids by human endothelial cell-leukocyte interactions. Proc Natl Acad Sci U S A 92:9475–9479. [CrossRef]
216. Serhan CN. 1989. On the relationship between leukotriene and lipoxin production by human neutrophils: evidence for differential metabolism of 15-HETE and 5-HETE. Biochim Biophys Acta 1004:158–168. [CrossRef]
217. Serhan CN. 1995. Leukocyte transmigration, chemotaxis, and oxygenated derivatives of arachidonic acid: when is chirality important? Am J Respir Cell Mol Biol 12:251–253. [CrossRef]
218. Brezinski ME, Serhan CN. 1990. Selective incorporation of (15S)-hydroxyeicosatetraenoic acid in phosphatidylinositol of human neutrophils: agonist-induced deacylation and transformation of stored hydroxyeicosanoids. Proc Natl Acad Sci U S A 87:6248–6252. [CrossRef]
219. Romano M, Serhan CN. 1992. Lipoxin generation by permeabilized human platelets. Biochemistry 31:8269–8277. [CrossRef]
220. Chiang N, Takano T, Arita M, Watanabe S, Serhan CN. 2003. A novel rat lipoxin A4 receptor that is conserved in structure and function. Br J Pharmacol 139:89–98. [CrossRef]
221. Fiore S, Maddox JF, Perez HD, Serhan CN. 1994. Identification of a human cDNA encoding a functional high affinity lipoxin A4 receptor. J Exp Med 180:253–260. [CrossRef]
222. Takano T, Fiore S, Maddox JF, Brady HR, Petasis NA, Serhan CN. 1997. Aspirin-triggered 15-epi-lipoxin A4 (LXA4) and LXA4 stable analogues are potent inhibitors of acute inflammation: evidence for anti-inflammatory receptors. J Exp Med 185:1693–1704. [CrossRef]
223. Maddox JF, Hachicha M, Takano T, Petasis NA, Fokin VV, Serhan CN. 1997. Lipoxin A4 stable analogs are potent mimetics that stimulate human monocytes and THP-1 cells via a G-protein-linked lipoxin A4 receptor. J Biol Chem 272:6972–6978. [CrossRef]
224. Ariel A, Chiang N, Arita M, Petasis NA, Serhan CN. 2003. Aspirin-triggered lipoxin A4 and B4 analogs block extracellular signal-regulated kinase-dependent TNF-α secretion from human T cells. J Immunol 170:6266–6272. [CrossRef]
225. Sodin-Semrl S, Taddeo B, Tseng D, Varga J, Fiore S. 2000. Lipoxin A4 inhibits IL-1β-induced IL-6, IL-8, and matrix metalloproteinase-3 production in human synovial fibroblasts and enhances synthesis of tissue inhibitors of metalloproteinases. J Immunol 164:2660–2666. [CrossRef]
226. Gronert K, Gewirtz A, Madara JL, Serhan CN. 1998. Identification of a human enterocyte lipoxin A4 receptor that is regulated by interleukin (IL)-13 and interferon γ and inhibits tumor necrosis factor α-induced IL-8 release. J Exp Med 187:1285–1294. [CrossRef]
227. Devchand PR, Arita M, Hong S, Bannenberg G, Moussignac RL, Gronert K, Serhan CN. 2003. Human ALX receptor regulates neutrophil recruitment in transgenic mice: roles in inflammation and host defense. FASEB J 17:652–659. [CrossRef]
228. Fukunaga K, Kohli P, Bonnans C, Fredenburgh LE, Levy BD. 2005. Cyclooxygenase 2 plays a pivotal role in the resolution of acute lung injury. J Immunol 174:5033–5039. [CrossRef]
229. Levy BD, De Sanctis GT, Devchand PR, Kim E, Ackerman K, Schmidt BA, Szczeklik W, Drazen JM, Serhan CN. 2002. Multi-pronged inhibition of airway hyper-responsiveness and inflammation by lipoxin A4. Nat Med 8:1018–1023. [CrossRef]
230. Paul-Clark MJ, Van Cao T, Moradi-Bidhendi N, Cooper D, Gilroy DW. 2004. 15-Epi-lipoxin A4-mediated induction of nitric oxide explains how aspirin inhibits acute inflammation. J Exp Med 200:69–78. [CrossRef]
231. Levy BD, Petasis NA, Serhan CN. 1997. Polyisoprenyl phosphates in intracellular signalling. Nature 389:985–990. [CrossRef]
232. József L, Zouki C, Petasis NA, Serhan CN, Filep JG. 2002. Lipoxin A4 and aspirin-triggered 15-epi-lipoxin A4 inhibit peroxynitrite formation, NF-κB and AP-1 activation, and IL-8 gene expression in human leukocytes. Proc Natl Acad Sci U S A 99:13266–13271. [CrossRef]
233. Filep JG, Beauchamp M, Baron C, Paquette Y. 1998. Peroxynitrite mediates IL-8 gene expression and production in lipopolysaccharide-stimulated human whole blood. J Immunol 161:5656–5662.
234. Zouki C, József L, Ouellet S, Paquette Y, Filep JG. 2001. Peroxynitrite mediates cytokine-induced IL-8 gene expression and production by human leukocytes. J Leukoc Biol 69:815–824.
235. Ohira T, Bannenberg G, Arita M, Takahashi M, Ge Q, Van Dyke TE, Stahl GL, Serhan CN, Badwey JA. 2004. A stable aspirin-triggered lipoxin A4 analog blocks phosphorylation of leukocyte-specific protein 1 in human neutrophils. J Immunol 173:2091–2098. [CrossRef]
236. Badr KF, DeBoer DK, Schwartzberg M, Serhan CN. 1989. Lipoxin A4 antagonizes cellular and in vivo actions of leukotriene D4 in rat glomerular mesangial cells: evidence for competition at a common receptor. Proc Natl Acad Sci U S A 86:3438–3442. [CrossRef]
237. Fiore S, Romano M, Reardon EM, Serhan CN. 1993. Induction of functional lipoxin A4 receptors in HL-60 cells. Blood 81:3395–3403.
238. Aliberti J, Serhan C, Sher A. 2002. Parasite-induced lipoxin A4 is an endogenous regulator of IL-12 production and immunopathology in Toxoplasma gondii infection. J Exp Med 196:1253–1262. [CrossRef]
239. Machado FS, Johndrow JE, Esper L, Dias A, Bafica A, Serhan CN, Aliberti J. 2006. Anti-inflammatory actions of lipoxin A4 and aspirin-triggered lipoxin are SOCS-2 dependent. Nat Med 12:330–334. [CrossRef]
240. Schaldach CM, Riby J, Bjeldanes LF. 1999. Lipoxin A4: a new class of ligand for the Ah receptor. Biochemistry 38:7594–7600. [CrossRef]
241. Maddox JF, Colgan SP, Clish CB, Petasis NA, Fokin VV, Serhan CN. 1998. Lipoxin B4 regulates human monocyte/neutrophil adherence and motility: design of stable lipoxin B4 analogs with increased biologic activity. FASEB J 12:487–494.
242. Patcha V, Wigren J, Winberg ME, Rasmusson B, Li J, Särndahl E. 2004. Differential inside-out activation of β2-integrins by leukotriene B4 and fMLP in human neutrophils. Exp Cell Res 300:308–319. [CrossRef]
243. Serhan CN, Takano T, Gronert K, Chiang N, Clish CB. 1999. Lipoxin and aspirin-triggered 15-epi-lipoxin cellular interactions anti-inflammatory lipid mediators. Clin Chem Lab Med 37:299–309. [CrossRef]
244. Soyombo O, Spur BW, Lee TH. 1994. Effects of lipoxin A4 on chemotaxis and degranulation of human eosinophils stimulated by platelet-activating factor and N-formyl-l-methionyl-l-leucyl-l-phenylalanine. Allergy 49:230–234. [CrossRef]
245. Maddox JF, Serhan CN. 1996. Lipoxin A4 and B4 are potent stimuli for human monocyte migration and adhesion: selective inactivation by dehydrogenation and reduction. J Exp Med 183:137–146. [CrossRef]
246. Chiang N, Gronert K, Clish CB, O’Brien JA, Freeman MW, Serhan CN. 1999. Leukotriene B4 receptor transgenic mice reveal novel protective roles for lipoxins and aspirin-triggered lipoxins in reperfusion. J Clin Invest 104:309–316. [CrossRef]
247. Morris T, Stables M, Hobbs A, de Souza P, Colville-Nash P, Warner T, Newson J, Bellingan G, Gilroy DW. 2009. Effects of low-dose aspirin on acute inflammatory responses in humans. J Immunol 183:2089–2096. [CrossRef]
248. Morris T, Stables M, Colville-Nash P, Newson J, Bellingan G, de Souza PM, Gilroy DW. 2010. Dichotomy in duration and severity of acute inflammatory responses in humans arising from differentially expressed proresolution pathways. Proc Natl Acad Sci U S A 107:8842–8847. [CrossRef]
249. Godson C, Mitchell S, Harvey K, Petasis NA, Hogg N, Brady HR. 2000. Cutting edge: lipoxins rapidly stimulate nonphlogistic phagocytosis of apoptotic neutrophils by monocyte-derived macrophages. J Immunol 164:1663–1667. [CrossRef]
250. Maderna P, Cottell DC, Berlasconi G, Petasis NA, Brady HR, Godson C. 2002. Lipoxins induce actin reorganization in monocytes and macrophages but not in neutrophils: differential involvement of Rho GTPases. Am J Pathol 160:2275–2283.
251. Bannenberg GL, Chiang N, Ariel A, Arita M, Tjonahen E, Gotlinger KH, Hong S, Serhan CN. 2005. Molecular circuits of resolution: formation and actions of resolvins and protectins. J Immunol 174:4345–4355. [CrossRef]
252. Freire-de-Lima CG, Xiao YQ, Gardai SJ, Bratton DL, Schiemann WP, Henson PM. 2006. Apoptotic cells, through transforming growth factor-β, coordinately induce anti-inflammatory and suppress pro-inflammatory eicosanoid and NO synthesis in murine macrophages. J Biol Chem 281:38376–38384. [CrossRef]
253. Mitchell S, Thomas G, Harvey K, Cottell D, Reville K, Berlasconi G, Petasis NA, Erwig L, Rees AJ, Savill J, Brady HR, Godson C. 2002. Lipoxins, aspirin-triggered epi-lipoxins, lipoxin stable analogues, and the resolution of inflammation: stimulation of macrophage phagocytosis of apoptotic neutrophils in vivo. J Am Soc Nephrol 13:2497–2507. [CrossRef]
254. Leonard MO, Hannan K, Burne MJ, Lappin DW, Doran P, Coleman P, Stenson C, Taylor CT, Daniels F, Godson C, Petasis NA, Rabb H, Brady HR. 2002. 15-Epi-16-(para-fluorophenoxy)-lipoxin A4-methyl ester, a synthetic analogue of 15-epi-lipoxin A4, is protective in experimental ischemic acute renal failure. J Am Soc Nephrol 13:1657–1662. [CrossRef]
255. McMahon B, Mitchell D, Shattock R, Martin F, Brady HR, Godson C. 2002. Lipoxin, leukotriene, and PDGF receptors cross-talk to regulate mesangial cell proliferation. FASEB J 16:1817–1819.
256. Sato Y, Kitasato H, Murakami Y, Hashimoto A, Endo H, Kondo H, Inoue M, Hayashi I. 2004. Down-regulation of lipoxin A4 receptor by thromboxane A2 signaling in RAW246.7 cells in vitro and bleomycin-induced lung fibrosis in vivo. Biomed Pharmacother 58:381–387. [CrossRef]
257. Wu SH, Wu XH, Lu C, Dong L, Chen ZQ. 2006. Lipoxin A4 inhibits proliferation of human lung fibroblasts induced by connective tissue growth factor. Am J Respir Cell Mol Biol 34:65–72. [CrossRef]
258. Serhan CN. 1994. Lipoxin biosynthesis and its impact in inflammatory and vascular events. Biochim Biophys Acta 1212:1–25. [CrossRef]
259. Tamaoki J, Tagaya E, Yamawaki I, Konno K. 1995. Lipoxin A4 inhibits cholinergic neurotransmission through nitric oxide generation in the rabbit trachea. Eur J Pharmacol 287:233–238. [CrossRef]
260. Hachicha M, Pouliot M, Petasis NA, Serhan CN. 1999. Lipoxin (LX)A4 and aspirin-triggered 15-epi-LXA4 inhibit tumor necrosis factor 1α-initiated neutrophil responses and trafficking: regulators of a cytokine-chemokine axis. J Exp Med 189:1923–1930. [CrossRef]
261. Pouliot M, Serhan CN. 1999. Lipoxin A4 and aspirin-triggered 15-epi-LXA4 inhibit tumor necrosis factor-α-initiated neutrophil responses and trafficking: novel regulators of a cytokine-chemokine axis relevant to periodontal diseases. J Periodontal Res 34:370–373. [CrossRef]
262. Machado FS, Johndrow JE, Esper L, Dias A, Bafica A, Serhan CN, Aliberti J. 2006. Anti-inflammatory actions of lipoxin A4 and aspirin-triggered lipoxin are SOCS-2 dependent. Nat Med 12:330–334. [CrossRef]
263. Munger KA, Montero A, Fukunaga M, Uda S, Yura T, Imai E, Kaneda Y, Valdivielso JM, Badr KF. 1999. Transfection of rat kidney with human 15-lipoxygenase suppresses inflammation and preserves function in experimental glomerulonephritis. Proc Natl Acad Sci U S A 96:13375–13380. [CrossRef]
264. O’Meara YM, Brady HR. 1997. Lipoxins, leukocyte recruitment and the resolution phase of acute glomerulonephritis. Kidney Int Suppl 58:S56–S61.
265. Karp CL, Flick LM, Yang R, Uddin J, Petasis NA. 2005. Cystic fibrosis and lipoxins. Prostaglandins Leukot Essent Fatty Acids 73:263–270. [CrossRef]
266. Pouliot M, Clish CB, Petasis NA, Van Dyke TE, Serhan CN. 2000. Lipoxin A4 analogues inhibit leukocyte recruitment to Porphyromonas gingivalis: a role for cyclooxygenase-2 and lipoxins in periodontal disease. Biochemistry 39:4761–4768. [CrossRef]
267. Levy BD, Bonnans C, Silverman ES, Palmer LJ, Marigowda G, Israel E, Severe Asthma Research Program, National Heart, Lung, and Blood Institute. 2005. Diminished lipoxin biosynthesis in severe asthma. Am J Respir Crit Care Med 172:824–830. [CrossRef]
268. Gronert K, Maheshwari N, Khan N, Hassan IR, Dunn M, Laniado Schwartzman M. 2005. A role for the mouse 12/15-lipoxygenase pathway in promoting epithelial wound healing and host defense. J Biol Chem 280:15267–15278. [CrossRef]
269. Schottelius AJ, Giesen C, Asadullah K, Fierro IM, Colgan SP, Bauman J, Guilford W, Perez HD, Parkinson JF. 2002. An aspirin-triggered lipoxin A4 stable analog displays a unique topical anti-inflammatory profile. J Immunol 169:7063–7070. [CrossRef]
270. Aliberti J, Hieny S, Reis e Sousa C, Serhan CN, Sher A. 2002. Lipoxin-mediated inhibition of IL-12 production by DCs: a mechanism for regulation of microbial immunity. Nat Immunol 3:76–82. [CrossRef]
271. Bafica A, Scanga CA, Serhan C, Machado F, White S, Sher A, Aliberti J. 2005. Host control of Mycobacterium tuberculosis is regulated by 5-lipoxygenase-dependent lipoxin production. J Clin Invest 115:1601–1606. [CrossRef]
272. Arita M, Yoshida M, Hong S, Tjonahen E, Glickman JN, Petasis NA, Blumberg RS, Serhan CN. 2005. Resolvin E1, an endogenous lipid mediator derived from omega-3 eicosapentaenoic acid, protects against 2,4,6-trinitrobenzene sulfonic acid-induced colitis. Proc Natl Acad Sci USA 102:7671–7676. [CrossRef]
273. Burr GO, Burr MM. 1973. Nutrition classics from The Journal of Biological Chemistry 82:345-67, 1929. A new deficiency disease produced by the rigid exclusion of fat from the diet. Nutr Rev 31:248–249.
274. Galli C, Risé P. 2009. Fish consumption, omega 3 fatty acids and cardiovascular disease. The science and the clinical trials. Nutr Health 20:11–20. [CrossRef]
275. Riediger ND, Othman RA, Suh M, Moghadasian MH. 2009. A systemic review of the roles of n-3 fatty acids in health and disease. J Am Diet Assoc 109:668–679. [CrossRef]
276. GISSI-Prevenzione Investigators (Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto miocardico). 1999. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Lancet 354:447–455.
277. León H, Shibata MC, Sivakumaran S, Dorgan M, Chatterley T, Tsuyuki RT. 2008. Effect of fish oil on arrhythmias and mortality: systematic review. BMJ 337:a2931. doi:10.1136/bmj.a2931. [CrossRef]
278. Ridker PM. 2009. The JUPITER trial: results, controversies, and implications for prevention. Circ Cardiovasc Qual Outcomes 2:279–285. [CrossRef]
279. De Caterina R, Caprioli R, Giannessi D, Sicari R, Galli C, Lazzerini G, Bernini W, Carr L, Rindi P. 1993. n-3 fatty acids reduce proteinuria in patients with chronic glomerular disease. Kidney Int 44:843–850. [CrossRef]
280. Lu Y, Hong S, Tjonahen E, Serhan CN. 2005. Mediator-lipidomics: databases and search algorithms for PUFA-derived mediators. J Lipid Res 46:790–802. [CrossRef]
281. Serhan CN, Yang R, Martinod K, Kasuga K, Pillai PS, Porter TF, Oh SF, Spite M. 2009. Maresins: novel macrophage mediators with potent antiinflammatory and proresolving actions. J Exp Med 206:15–23. [CrossRef]
282. Serhan CN. 2008. Controlling the resolution of acute inflammation: a new genus of dual anti-inflammatory and proresolving mediators. J Periodontol 79(Suppl):1520–1526. [CrossRef]
283. Serhan CN. 2008. Systems approach with inflammatory exudates uncovers novel anti-inflammatory and pro-resolving mediators. Prostaglandins Leukot Essent Fatty Acids 79:157–163. [CrossRef]
284. Arita M, Clish CB, Serhan CN. 2005. The contributions of aspirin and microbial oxygenase to the biosynthesis of anti-inflammatory resolvins: novel oxygenase products from omega-3 polyunsaturated fatty acids. Biochem Biophys Res Commun 338:149–157. [CrossRef]
285. Arita M, Bianchini F, Aliberti J, Sher A, Chiang N, Hong S, Yang R, Petasis NA, Serhan CN. 2005. Stereochemical assignment, antiinflammatory properties, and receptor for the omega-3 lipid mediator resolvin E1. J Exp Med 201:713–722. [CrossRef]
286. Serhan CN. 2006. Novel chemical mediators in the resolution of inflammation: resolvins and protectins. Anesthesiol Clin 24:341–364. [CrossRef]
287. Campbell EL, Louis NA, Tomassetti SE, Canny GO, Arita M, Serhan CN, Colgan SP. 2007. Resolvin E1 promotes mucosal surface clearance of neutrophils: a new paradigm for inflammatory resolution. FASEB J 21:3162–3170. [CrossRef]
288. Gronert K, Kantarci A, Levy BD, Clish CB, Odparlik S, Hasturk H, Badwey JA, Colgan SP, Van Dyke TE, Serhan CN. 2004. A molecular defect in intracellular lipid signaling in human neutrophils in localized aggressive periodontal tissue damage. J Immunol 172:1856–1861. [CrossRef]
289. Arita M, Ohira T, Sun YP, Elangovan S, Chiang N, Serhan CN. 2007. Resolvin E1 selectively interacts with leukotriene B4 receptor BLT1 and ChemR23 to regulate inflammation. J Immunol 178:3912–3917. [CrossRef]
290. Haworth O, Cernadas M, Yang R, Serhan CN, Levy BD. 2008. Resolvin E1 regulates interleukin 23, interferon-γ and lipoxin A4 to promote the resolution of allergic airway inflammation. Nat Immunol 9:873–879. [CrossRef]
291. Schwab JM, Chiang N, Arita M, Serhan CN. 2007. Resolvin E1 and protectin D1 activate inflammation-resolution programmes. Nature 447:869–874. [CrossRef]
292. Tjonahen E, Oh SF, Siegelman J, Elangovan S, Percarpio KB, Hong S, Arita M, Serhan CN. 2006. Resolvin E2: identification and anti-inflammatory actions: pivotal role of human 5-lipoxygenase in resolvin E series biosynthesis. Chem Biol 13:1193–1202. [CrossRef]
293. Dona M, Fredman G, Schwab JM, Chiang N, Arita M, Goodarzi A, Cheng G, von Andrian UH, Serhan CN. 2008. Resolvin E1, an EPA-derived mediator in whole blood, selectively counterregulates leukocytes and platelets. Blood 112:848–855. [CrossRef]
294. Hasturk H, Kantarci A, Ohira T, Arita M, Ebrahimi N, Chiang N, Petasis NA, Levy BD, Serhan CN, Van Dyke TE. 2006. RvE1 protects from local inflammation and osteoclast- mediated bone destruction in periodontitis. FASEB J 20:401–403.
295. Zabel BA, Ohyama T, Zuniga L, Kim JY, Johnston B, Allen SJ, Guido DG, Handel TM, Butcher EC. 2006. Chemokine-like receptor 1 expression by macrophages in vivo: regulation by TGF-β and TLR ligands. Exp Hematol 34:1106–1114. [CrossRef]
296. Cash JL, Hart R, Russ A, Dixon JP, Colledge WH, Doran J, Hendrick AG, Carlton MB, Greaves DR. 2008. Synthetic chemerin-derived peptides suppress inflammation through ChemR23. J Exp Med 205:767–775. [CrossRef]
297. Krishnamoorthy S, Recchiuti A, Chiang N, Yacoubian S, Lee CH, Yang R, Petasis NA, Serhan CN. 2010. Resolvin D1 binds human phagocytes with evidence for proresolving receptors. Proc Natl Acad Sci U S A 107:1660–1665. [CrossRef]
298. Spite M, Norling LV, Summers L, Yang R, Cooper D, Petasis NA, Flower RJ, Perretti M, Serhan CN. 2009. Resolvin D2 is a potent regulator of leukocytes and controls microbial sepsis. Nature 461:1287–1291. [CrossRef]
299. Sun YP, Oh SF, Uddin J, Yang R, Gotlinger K, Campbell E, Colgan SP, Petasis NA, Serhan CN. 2007. Resolvin D1 and its aspirin-triggered 17R epimer. Stereochemical assignments, anti-inflammatory properties, and enzymatic inactivation. J Biol Chem 282:9323–9334. [CrossRef]
300. Chiang N, Dalli J, Colas RA, Serhan CN. 2015. Identification of resolvin D2 receptor mediating resolution of infections and organ protection. J Exp Med 212:1203–1217. [CrossRef]
301. Duffield JS, Hong S, Vaidya VS, Lu Y, Fredman G, Serhan CN, Bonventre JV. 2006. Resolvin D series and protectin D1 mitigate acute kidney injury. J Immunol 177:5902–5911. [CrossRef]
302. Levy BD, Kohli P, Gotlinger K, Haworth O, Hong S, Kazani S, Israel E, Haley KJ, Serhan CN. 2007. Protectin D1 is generated in asthma and dampens airway inflammation and hyperresponsiveness. J Immunol 178:496–502. [CrossRef]
303. Ariel A, Li PL, Wang W, Tang WX, Fredman G, Hong S, Gotlinger KH, Serhan CN. 2005. The docosatriene protectin D1 is produced by TH2 skewing and promotes human T cell apoptosis via lipid raft clustering. J Biol Chem 280:43079–43086. [CrossRef]
304. Mukherjee PK, Marcheselli VL, Barreiro S, Hu J, Bok D, Bazan NG. 2007. Neurotrophins enhance retinal pigment epithelial cell survival through neuroprotectin D1 signaling. Proc Natl Acad Sci U S A 104:13152–13157. [CrossRef]
305. Mukherjee PK, Marcheselli VL, de Rivero Vaccari JC, Gordon WC, Jackson FE, Bazan NG. 2007. Photoreceptor outer segment phagocytosis attenuates oxidative stress-induced apoptosis with concomitant neuroprotectin D1 synthesis. Proc Natl Acad Sci U S A 104:13158–13163. [CrossRef]
306. Mukherjee PK, Marcheselli VL, Serhan CN, Bazan NG. 2004. Neuroprotectin D1: a docosahexaenoic acid-derived docosatriene protects human retinal pigment epithelial cells from oxidative stress. Proc Natl Acad Sci U S A 101:8491–8496. [CrossRef]
307. Lukiw WJ, Cui JG, Marcheselli VL, Bodker M, Botkjaer A, Gotlinger K, Serhan CN, Bazan NG. 2005. A role for docosahexaenoic acid-derived neuroprotectin D1 in neural cell survival and Alzheimer disease. J Clin Invest 115:2774–2783. [CrossRef]
308. Vedin I, Cederholm T, Freund Levi Y, Basun H, Garlind A, Faxén Irving G, Jönhagen ME, Vessby B, Wahlund LO, Palmblad J. 2008. Effects of docosahexaenoic acid-rich n-3 fatty acid supplementation on cytokine release from blood mononuclear leukocytes: the OmegAD study. Am J Clin Nutr 87:1616–1622.
309. Nelson DR, Koymans L, Kamataki T, Stegeman JJ, Feyereisen R, Waxman DJ, Waterman MR, Gotoh O, Coon MJ, Estabrook RW, Gunsalus IC, Nebert DW. 1996. P450 superfamily: update on new sequences, gene mapping, accession numbers and nomenclature. Pharmacogenetics 6:1–42. [CrossRef]
310. Scarborough PE, Ma J, Qu W, Zeldin DC. 1999. P450 subfamily CYP2J and their role in the bioactivation of arachidonic acid in extrahepatic tissues. Drug Metab Rev 31:205–234. [CrossRef]
311. Roman RJ. 2002. P-450 metabolites of arachidonic acid in the control of cardiovascular function. Physiol Rev 82:131–185. [CrossRef]
312. Zhang Y, Oltman CL, Lu T, Lee HC, Dellsperger KC, VanRollins M. 2001. EET homologs potently dilate coronary microvessels and activate BKCa channels. Am J Physiol Heart Circ Physiol 280:H2430–H2440.
313. Wang MH, Guan H, Nguyen X, Zand BA, Nasjletti A, Laniado-Schwartzman M. 1999. Contribution of cytochrome P-450 4A1 and 4A2 to vascular 20-hydroxyeicosatetraenoic acid synthesis in rat kidneys. Am J Physiol 276:F246–F253.
314. Kikuchi Y, Miyauchi M, Oomori K, Kita T, Kizawa I, Kato K. 1986. Inhibition of human ovarian cancer cell growth in vitro and in nude mice by prostaglandin D2. Cancer Res 46:3364–3366.
315. Bednar MM, Gross CE, Balazy MK, Belosludtsev Y, Colella DT, Falck JR, Balazy M. 2000. 16(R)-hydroxy-5,8,11,14-eicosatetraenoic acid, a new arachidonate metabolite in human polymorphonuclear leukocytes. Biochem Pharmacol 60:447–455. [CrossRef]
316. Fleming I. 2007. DiscrEET regulators of homeostasis: epoxyeicosatrienoic acids, cytochrome P450 epoxygenases and vascular inflammation. Trends Pharmacol Sci 28:448–452. [CrossRef]
317. Moreno JJ. 2009. New aspects of the role of hydroxyeicosatetraenoic acids in cell growth and cancer development. Biochem Pharmacol 77:1–10. [CrossRef]
318. Spector AA, Norris AW. 2007. Action of epoxyeicosatrienoic acids on cellular function. Am J Physiol Cell Physiol 292:C996–C1012. [CrossRef]
319. Inceoglu B, Jinks SL, Ulu A, Hegedus CM, Georgi K, Schmelzer KR, Wagner K, Jones PD, Morisseau C, Hammock BD. 2008. Soluble epoxide hydrolase and epoxyeicosatrienoic acids modulate two distinct analgesic pathways. Proc Natl Acad Sci U S A 105:18901–18906. [CrossRef]
320. Inceoglu B, Schmelzer KR, Morisseau C, Jinks SL, Hammock BD. 2007. Soluble epoxide hydrolase inhibition reveals novel biological functions of epoxyeicosatrienoic acids (EETs). Prostaglandins Other Lipid Mediat 82:42–49. [CrossRef]
321. Node K, Huo Y, Ruan X, Yang B, Spiecker M, Ley K, Zeldin DC, Liao JK. 1999. Anti-inflammatory properties of cytochrome P450 epoxygenase-derived eicosanoids. Science 285:1276–1279. [CrossRef]
322. Liu Y, Zhang Y, Schmelzer K, Lee TS, Fang X, Zhu Y, Spector AA, Gill S, Morisseau C, Hammock BD, Shyy JY. 2005. The antiinflammatory effect of laminar flow: the role of PPARγ, epoxyeicosatrienoic acids, and soluble epoxide hydrolase. Proc Natl Acad Sci U S A 102:16747–16752. [CrossRef]
323. Briggs WH, Xiao H, Parkin KL, Shen C, Goldman IL. 2000. Differential inhibition of human platelet aggregation by selected Allium thiosulfinates. J Agric Food Chem 48:5731–5735. [CrossRef]
324. Fitzpatrick FA, Ennis MD, Baze ME, Wynalda MA, McGee JE, Liggett WF. 1986. Inhibition of cyclooxygenase activity and platelet aggregation by epoxyeicosatrienoic acids. Influence of stereochemistry. J Biol Chem 261:15334–15338.
325. Heizer ML, McKinney JS, Ellis EF. 1991. 14,15-Epoxyeicosatrienoic acid inhibits platelet aggregation in mouse cerebral arterioles. Stroke 22:1389–1393. [CrossRef]
326. Node K, Ruan XL, Dai J, Yang SX, Graham L, Zeldin DC, Liao JK. 2001. Activation of Gαs mediates induction of tissue-type plasminogen activator gene transcription by epoxyeicosatrienoic acids. J Biol Chem 276:15983–15989. [CrossRef]
327. Behm DJ, Ogbonna A, Wu C, Burns-Kurtis CL, Douglas SA. 2009. Epoxyeicosatrienoic acids function as selective, endogenous antagonists of native thromboxane receptors: identification of a novel mechanism of vasodilation. J Pharmacol Exp Ther 328:231–239. [CrossRef]
328. Hill E, Fitzpatrick F, Murphy RC. 1992. Biological activity and metabolism of 20-hydroxyeicosatetraenoic acid in the human platelet. Br J Pharmacol 106:267–274. [CrossRef]
329. Buckley CD, Gilroy DW, Serhan CN, Stockinger B, Tak PP. 2013. The resolution of inflammation. Nat Rev Immunol 13:59–66. [CrossRef]
330. Serhan CN, Brain SD, Buckley CD, Gilroy DW, Haslett C, O’Neill LA, Perretti M, Rossi AG, Wallace JL. 2007. Resolution of inflammation: state of the art, definitions and terms. FASEB J 21:325–332. [CrossRef]
331. Kurzrok R, Lieb CC. 1930. Biochemical studies of human semen. II. The action of semen on the human uterus. Proc Soc Exp Biol Med 28:268–272. [CrossRef]
microbiolspec.MCHD-0035-2016.citations
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/content/journal/microbiolspec/10.1128/microbiolspec.MCHD-0035-2016
2016-11-11
2017-09-26

Abstract:

Lipids are potent signaling molecules that regulate a multitude of cellular responses, including cell growth and death and inflammation/infection, via receptor-mediated pathways. Derived from polyunsaturated fatty acids (PUFAs), such as arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), each lipid displays unique properties, thus making their role in inflammation distinct from that of other lipids derived from the same PUFA. This diversity arises from their synthesis, which occurs via discrete enzymatic pathways and because they elicit responses via different receptors. This review will collate the bioactive lipid research to date and summarize the major pathways involved in their biosynthesis and role in inflammation. Specifically, lipids derived from AA (prostanoids, leukotrienes, 5-oxo-6,8,11,14-eicosatetraenoic acid, lipoxins, and epoxyeicosatrienoic acids), EPA (E-series resolvins), and DHA (D-series resolvins, protectins, and maresins) will be discussed herein.

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