Specialized proresolving mediator targets for RvE1 and RvD1 in peripheral blood and mechanisms of resolution

Biochemical Journal

Volumn 437, Issue 2, 2011, Pages 185-197

  Fredman, Gabrielle ^a   Serhan, Charles N ^a  

^a BRIGHAM AND WOMEN S HOSPITAL   (United States)

Author keywords

Lipid mediator; MicroRNA; Omega 3 fatty acid; Platelet; Resolution

Indexed keywords

ACETYLSALICYLIC ACID; AUTACOID; CHEMOKINE; CYTOKINE; LIPID; MEDIATOR COMPLEX; MICRORNA; OMEGA 3 FATTY ACID; POLYUNSATURATED FATTY ACID; RESOLVIN D1; RESOLVIN E1; TRANSCRIPTION FACTOR; UNCLASSIFIED DRUG;

BIOSYNTHESIS; CARDIOVASCULAR DISEASE; GENE MAPPING; HEART INFARCTION; HOMEOSTASIS; HUMAN; INFLAMMATION; LOW DRUG DOSE; MACROPHAGE; MONOCYTE; NONHUMAN; PRIORITY JOURNAL; REGULATORY MECHANISM; REVIEW; SIGNAL TRANSDUCTION; SMOOTH MUSCLE FIBER; STROKE; THROMBOCYTE; UNSTABLE ANGINA PECTORIS;

ANIMALS; AUTACOIDS; BLOOD PLATELETS; DOCOSAHEXAENOIC ACIDS; EICOSAPENTAENOIC ACID; HOMEOSTASIS; HUMANS; INFLAMMATION; INFLAMMATION MEDIATORS; LIPOXINS; MACROPHAGES; MICE; MICRORNAS; RATS;

EID: 79959720828     PISSN: 02646021     EISSN: 14708728     Source Type: Journal    
DOI: 10.1042/BJ20110327     Document Type: Review

References (136)

1. Kumar, V., Abbas, A. K., Fausto, N., Robbins, S. L. and Cotran, R. S. (2005) Robbins and Cotran Pathologic Basis of Disease. Elsevier/Saunders, Philadelphia
2. de Pablo, P., Chapple, I. L., Buckley, C. D. and Dietrich, T. (2009) Periodontitis in systemic rheumatic diseases. Nat. Rev. Rheumatol. 5, 218-224
3. Bannenberg, G. L., Chiang, N., Ariel, A., Arita, M., Tjonahen, E., Gotlinger, K. H., Hong, S. and Serhan, C. N. (2005) Molecular circuits of resolution: formation and actions of resolvins and protectins. J. Immunol. 174, 4345-4355
4. Marcus, A. J. (1999) Platelets: their role in hemostasis, thrombosis, and inflammation. In Inflammation: Basic Principles and Clinical Correlates (J. I. Gallin and R. Snyderman, eds), pp. 77-95, Lippincott, Williams & Wilkins, Philadelphia
5. Willoughby, D. A., Moore, A. R., Colville-Nash, P. R. and Gilroy, D. (2000) Resolution of inflammation. Int. J. Immunopharmacol. 22, 1131-1135
6. Serhan, C. N. (2007) Resolution phase of inflammation: novel endogenous anti-inflammatory and proresolving lipid mediators and pathways. Annu. Rev. Immunol. 25, 101-137
7. Bannenberg, G. and Serhan, C. N. (2010) Specialized pro-resolving lipid mediators in the inflammatory response: an update. Biochim. Biophys. Acta 1801, 1260-1273
8. Spite, M. and Serhan, C. N. (2010) Novel lipid mediators promote resolution of acute inflammation: impact of aspirin and statins. Circ. Res. 107, 1170-1184
9. Oh, S. F., Pillai, P. S., Recchiuti, A., Yang, R. and Serhan, C. N. (2011) Pro-resolving actions and stereoselective biosynthesis of 18S E-series resolvins in human leukocytes and murine inflammation. J. Clin. Invest. 121, 569-581
10. Serhan, C. N. (2005) Special issue on lipoxins and aspirin-triggered lipoxins. Prostaglandins Leukotrienes Essent. Fatty Acids 73, 139-321
11. Samuelsson, B., Dahlen, S. E., Lindgren, J. A., Rouzer, C. A. and Serhan, C. N. (1987) Leukotrienes and lipoxins: structures, biosynthesis, and biological effects. Science 237, 1171-1176
12. Schwab, J. M., Chiang, N., Arita, M. and Serhan, C. N. (2007) Resolvin E1 and protectin D1 activate inflammation-resolution programmes. Nature 447, 869-874
13. Serhan, C. N., Clish, C. B., Brannon, J., Colgan, S. P., Chiang, N. and 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
14. Serhan, C. N., Hong, S., Gronert, K., Colgan, S. P., Devchand, P. R., Mirick, G. and Moussignac, R. L. (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
15. Hong, S., Gronert, K., Devchand, P. R., Moussignac, R. L. and Serhan, C. N. (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
16. Serhan, C. N., Gotlinger, K., Hong, S., Lu, Y., Siegelman, J., Baer, T., Yang, R., Colgan, S. P. and Petasis, N. A. (2006) Anti-inflammatory actions of neuroprotectin D1/protectin D1 and its natural stereoisomers: assignments of dihydroxy-containing docosatrienes. J. Immunol. 176, 1848-1859
17. Arita, M., Bianchini, F., Aliberti, J., Sher, A., Chiang, N., Hong, S., Yang, R., Petasis, N. A. and Serhan, C. N. (2005) Stereochemical assignment, anti-inflammatory properties, and receptor for the omega-3 lipid mediator resolvin E1. J. Exp. Med. 201, 713-722
18. Serhan, C. N., Chiang, N. and Van Dyke, T. E. (2008) Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators. Nat. Rev. Immunol. 8, 349-361
19. Campbell, E. L., Louis, N. A., Tomassetti, S. E., Canny, G. O., Arita, M., Serhan, C. N. and Colgan, S. P. (2007) Resolvin E1 promotes mucosal surface clearance of neutrophils: a new paradigm for inflammatory resolution. FASEB J. 21, 3162-3170 (Pubitemid 47565535)
20. Ariel, A., Fredman, G., Sun, Y. P., Kantarci, A., Van Dyke, T. E., Luster, A. D. and Serhan, C. N. (2006) Apoptotic neutrophils and T cells sequester chemokines during immune response resolution through modulation of CCR5 expression. Nat. Immunol. 7, 1209-1216
21. Arita, M., Ohira, T., Sun, Y. P., Elangovan, S., Chiang, N. and Serhan, C. N. (2007) Resolvin E1 selectively interacts with leukotriene B4 receptor BLT1 and ChemR23 to regulate inflammation. J. Immunol. 178, 3912-3917
22. Ohira, T., Arita, M., Omori, K., Recchiuti, A., Van Dyke, T. E. and Serhan, C. N. (2009) Resolvin E1 receptor activation signals phosphorylation and phagocytosis. J. Biol. Chem. 285, 3451-3461
23. Starosta, V., Pazdrak, K., Boldogh, I., Svider, T. and Kurosky, A. (2008) Lipoxin A4 counterregulates GM-CSF signaling in eosinophilic granulocytes. J. Immunol. 181, 8688-8699
24. Krishnamoorthy, S., Recchiuti, A., Chiang, N., Yacoubian, S., Lee, C.-H., Yang, R., Petasis, N. A. and Serhan, C. N. (2010) Resolvin D1 binds human phagocytes with evidence for pro-resolving receptors. Proc. Natl. Acad. Sci. U.S.A. 107, 1660-1665
25. Riviere, S., Challet, L., Fluegge, D., Spehr, M. and Rodriguez, I. (2009) Formyl peptide receptor-like proteins are a novel family of vomeronasal chemosensors. Nature 459, 574-577
26. Perretti, M. and D'Acquisto, F. (2009) Annexin A1 and glucocorticoids as effectors of the resolution of inflammation. Nat. Rev. Immunol. 9, 62-70
27. Kasuga, K., Yang, R., Porter, T. F., Agrawal, N., Petasis, N. A., Irimia, D., Toner, M. and Serhan, C. N. (2008) Rapid appearance of resolvin precursors in inflammatory exudates: novel mechanisms in resolution. J. Immunol. 181, 8677-8687
28. Varani, J. and Ward, P. A. (1994) Mechanisms of endothelial cell injury in acute inflammation. Shock 2, 311-319
29. Dallegri, F. and Ottonello, L. (1997) Tissue injury in neutrophilic inflammation. Inflammation Res. 46, 382-391 (Pubitemid 27478595)
30. Weiss, S. J. (1989) Tissue destruction by neutrophils. N. Engl. J. Med. 320, 365-376
31. Han, J. and Ulevitch, R. J. (2005) Limiting inflammatory responses during activation of innate immunity. Nat. Immunol. 6, 1198-1205
32. Larsson, S. C., Kumlin, M., Ingelman-Sundberg, M. and Wolk, A. (2004) Dietary long-chain n-3 fatty acids for the prevention of cancer: a review of potential mechanisms. Am. J. Clin. Nutr. 79, 935-945
33. Lukiw, W. J. and Bazan, N. G. (2008) Docosahexaenoic acid and the aging brain. J. Nutr. 138, 2510-2514
34. 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
35. Albert, C. M., Hennekens, C. H., O'Donnell, C. J., Ajani, U. A., Carey, V. J., Willett, W. C., Ruskin, J. N. and Manson, J. E. (1998) Fish consumption and risk of sudden cardiac death. JAMA, J. Am. Med. Assoc. 279, 23-28 (Pubitemid 28070546)
36. Albert, C. M., Campos, H., Stampfer, M. J., Ridker, P. M., Manson, J. E., Willett, W. C. and Ma, J. (2002) Blood levels of long-chain n-3 fatty acids and the risk of sudden death. N. Engl. J. Med. 346, 1113-1118
37. Harris, W. S. and Von Schacky, C. (2004) The omega-3 index: a new risk factor for death from coronary heart disease? Prev. Med. 39, 212-220 (Pubitemid 38797975)
38. Leon, H., Shibata, M. C., Sivakumaran, S., Dorgan, M., Chatterley, T. and Tsuyuki, R. T. (2008) Effect of fish oil on arrhythmias and mortality: systematic review. BMJ 337, a2931
39. Bang, H. O., Dyerberg, J. and Nielsen, A. B. (1971) Plasma lipid and lipoprotein pattern in Greenlandic West-coast Eskimos. Lancet 1, 1143-1145
40. Bang, H. O., Dyerberg, J. and Hjoorne, N. (1976) The composition of food consumed by Greenland Eskimos. Acta Med. Scand. 200, 69-73
41. Dyerberg, J. and Bang, H. O. (1979) Lipid metabolism, atherogenesis, and haemostasis in Eskimos: the role of the prostaglandin-3 family. Haemostasis 8, 227-233
42. Bang, H. O., Dyerberg, J. and Sinclair, H. M. (1980) The composition of the Eskimo food in north western Greenland. Am. J. Clin. Nutr. 33, 2657-2661
43. Dyerberg, J. and Bang, H. O. (1979) Haemostatic function and platelet polyunsaturated fatty acids in Eskimos. Lancet 2, 433-435
44. Dyerberg, J., Bang, H. O., Stoffersen, E., Moncada, S. and Vane, J. R. (1978) Eicosapentaenoic acid and prevention of thrombosis and atherosclerosis? Lancet 2, 117-119
45. Needleman, P., Moncada, S., Bunting, S., Vane, J. R., Hamberg, M. and Samuelsson, B. (1976) Identification of an enzyme in platelet microsomes which generates thromboxane A2 from prostaglandin endoperoxides. Nature 261, 558-560
46. Hamberg, M., Svensson, J. and 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
47. Simopoulos, A. P. (1991) Omega-3 fatty acids in health and disease and in growth and development. Am. J. Clin. Nutr. 54, 438-463
48. Needleman, P., Raz, A., Minkes, M. S., Ferrendelli, J. A. and Sprecher, H. (1979) Triene prostaglandins: prostacyclin and thromboxane biosynthesis and unique biological properties. Proc. Natl. Acad. Sci. U.S.A. 76, 944-948
49. Needleman, P., Wyche, A., LeDuc, L., Sankarappe, S. K., Jakschik, B. A. and Sprecher, H. (1981) Fatty acids as sources of potential 'magic bullets' for the modification of platelet and vascular function. Prog. Lipid Res. 20, 415-422
50. Needleman, P., Minkes, M. and Raz, A. (1976) Thromboxanes: selective biosynthesis and distinct biological properties. Science 193, 163-165
51. Tavazzi, L., Maggioni, A. P., Marchioli, R., Barlera, S., Franzosi, M. G., Latini, R., Lucci, D., Nicolosi, G. L., Porcu, M. and Tognoni, G. (2008) Effect of n-3 polyunsaturated fatty acids in patients with chronic heart failure (the GISSI-HF trial): a randomized, double-blind, placebo-controlled trial. Lancet 372, 1223-1230
52. Marchioli, R., Barzi, F., Bomba, E., Chieffo, C., Di Gregorio, D., Di Mascio, R., Franzosi, M. G., Geraci, E., Levantesi, G., Maggioni, A. P. et al. (2002) Early protection against sudden death by n-3 polyunsaturated fatty acids after myocardial infarction: time-course analysis of the results of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI)-Prevenzione. Circulation 105, 1897-1903 (Pubitemid 34437615)
53. Vane, J. R. (1976) The mode of action of aspirin and similar compounds. J. Allergy Clin. Immunol. 58, 691-712
54. Vane, J. R. and Botting, R. M. (2003) The mechanism of action of aspirin. Thromb. Res. 110, 255-258
55. Gilroy, D. W., Colville-Nash, P. R., Willis, D., Chivers, J., Paul-Clark, M. J. and Willoughby, D. A. (1999) Inducible cyclooxygenase may have anti-inflammatory properties. Nat. Med. 5, 698-701
56. Chiang, N., Bermudez, E. A., Ridker, P. M., Hurwitz, S. and Serhan, C. N. (2004) Aspirin triggers antiinflammatory 15-epi-lipoxin A4 and inhibits thromboxane in a randomized human trial. Proc. Natl. Acad. Sci. U.S.A. 101, 15178-15183
57. Chiang, N., Hurwitz, S., Ridker, P. M. and Serhan, C. N. (2006) Aspirin has a gender-dependent impact on antiinflammatory 15-epi-lipoxin A4 formation: a randomized human trial. Arterioscler. Thromb. Vasc. Biol. 26, e14-e17
58. Morris, T., Stables, M., Hobbs, A., de Souza, P., Colville-Nash, P., Warner, T., Newson, J., Bellingan, G. and Gilroy, D. W. (2009) Effects of low-dose aspirin on acute inflammatory responses in humans. J. Immunol. 183, 2089-2096
59. Morris, T., Stables, M., Colville-Nash, P., Newson, J., Bellingan, G., de Souza, P. M. and Gilroy, D. W. (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
60. Serhan, C. N., Clish, C. B., Brannon, J., Colgan, S. P., Gronert, K. and Chiang, N. (2000) Anti-microinflammatory lipid signals generated from dietary N-3 fatty acids via cyclooxygenase-2 and transcellular processing: a novel mechanism for NSAID and N-3 PUFA therapeutic actions. J. Physiol. Pharmacol. 51, 643-654
61. Haas-Stapleton, E. H., Lu, Y., Hong, S., Arita, M., Favoreto, S., Nigam, S., Serhan, C. N. and Agabian, N. (2007) Candida albicans modulates host defense by biosynthesizing the pro-resolving mediator Resolvin E1. PLoS ONE 2, e1316
62. Hasturk, H., Kantarci, A., Ohira, T., Arita, M., Ebrahimi, N., Chiang, N., Petasis, N. A., Levy, B. D., Serhan, C. N. and Van Dyke, T. E. (2006) RvE1 protects from local inflammation and osteoclast- mediated bone destruction in periodontitis. FASEB J. 20, 401-403
63. Hasturk, H., Kantarci, A., Goguet-Surmenian, E., Blackwood, A., Andry, C., Serhan, C. N. and Van Dyke, T. E. (2007) Resolvin E1 regulates inflammation at the cellular and tissue level and restores tissue homeostasis in vivo. J. Immunol. 179, 7021-7029
64. Arita, M., Yoshida, M., Hong, S., Tjonahen, E., Glickman, J. N., Petasis, N. A., Blumberg, R. S. and Serhan, C. N. (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. U.S.A. 102, 7671-7676
65. Li, N., He, J., Schwartz, C. E., Gjorstrup, P. and Bazan, H. E. (2010) Resolvin e1 improves tear production and decreases inflammation in a dry eye mouse model. J. Ocul. Pharmacol. Ther. 26, 431-439
66. Dona, M., Fredman, G., Schwab, J. M., Chiang, N., Arita, M., Goodarzi, A., Cheng, G., von Andrian, U. H. and Serhan, C. N. (2008) Resolvin E1, an EPA-derived mediator in whole blood, selectively counterregulates leukocytes and platelets. Blood. 112, 848-855
67. Marcus, A. J. (1990) Stratton lecture 1989. Thrombosis and inflammation as multicellular processes: pathophysiologic significance of transcellular metabolism. Blood 76, 1903-1907
68. Gawaz, M., Langer, H. and May, A. E. (2005) Platelets in inflammation and atherogenesis. J. Clin. Invest. 115, 3378-3384
69. Knapp, H. R., Reilly, I. A. G., Alessandrini, P. and FitzGerald, G. A. (1986) In vivo indexes of platelet and vascular function during fish-oil administration in patients with atherosclerosis. N. Engl. J. Med. 314, 937-942
70. Chen, P., Fenet, B., Michaud, S., Tomczyk, N., Vericel, E., Lagarde, M. and Guichardant, M. (2009) Full characterization of PDX, a neuroprotectin/ protectin D1 isomer, which inhibits blood platelet aggregation. FEBS Lett. 583, 3478-3484
71. Chen, P., Vericel, E., Lagarde, M. and Guichardant, M. (2011) Poxytrins, a class of oxygenated products from polyunsaturated fatty acids, potently inhibit blood platelet aggregation. FASEB J. 25, 382-388
72. Fredman, G., Van Dyke, T. E. and Serhan, C. N. (2010) Resolvin E1 regulates adenosine diphosphate activation of human platelets. Arterioscler. Thromb. Vasc. Biol. 30, 2005-2013
73. Michelson, A. D. (2007) Platelets. Academic Press/Elsevier, Amsterdam
74. Gachet, C. (2008) P2 receptors, platelet function and pharmacological implications. Thromb. Haemost. 99, 466-472
75. Bhatt, D. L. (2008) Platelets in cardiovascular disease. Imperial College Press, London
76. Michelson, A. D. (2010) Antiplatelet therapies for the treatment of cardiovascular disease. Nat. Rev. Drug Discovery 9, 154-169
77. Ridker, P. M. (2003) Clinical application of C-reactive protein for cardiovascular disease detection and prevention. Circulation 107, 363-369
78. Ho, K. J., Owens, C. D., Longo, T., Sui, X. X., Ifantides, C. and Conte, M. S. (2008) C-reactive protein and vein graft disease: evidence for a direct effect on smooth muscle cell phenotype via modulation of PDGF receptor-beta. Am. J. Physiol. Heart Circ. Physiol. 295, H1132-H1140
79. Ho, K. J., Spite, M., Owens, C. D., Lancero, H., Kroemer, A. H., Pande, R., Creager, M. A., Serhan, C. N. and Conte, M. S. (2010) Aspirin-triggered lipoxin and resolvin E1 modulate vascular smooth muscle phenotype and correlate with peripheral atherosclerosis. Am. J. Pathol. 177, 2116-2123
80. Braunwald, E. (1997) Shattuck lecture: cardiovascular medicine at the turn of the millennium: triumphs, concerns, and opportunities. N. Engl. J. Med. 337, 1360-1369
81. Hansson, G. K. and Libby, P. (2006) The immune response in atherosclerosis: a double-edged sword. Nat. Rev. Immunol. 6, 508-519
82. Tabas, I. (2010) Macrophage death and defective inflammation resolution in atherosclerosis. Nat. Rev. Immunol. 10, 36-46
83. Li, S., Sun, Y., Liang, C. P., Thorp, E. B., Han, S., Jehle, A. W., Saraswathi, V., Pridgen, B., Kanter, J. E., Li, R. et al. (2009) Defective phagocytosis of apoptotic cells by macrophages in atherosclerotic lesions of ob/ob mice and reversal by a fish oil diet. Circ. Res. 105, 1072-1082
84. Merched, A. J., Ko, K., Gotlinger, K. H., Serhan, C. N. and Chan, L. (2008) Atherosclerosis: evidence for impairment of resolution of vascular inflammation governed by specific lipid mediators. FASEB J. 22, 3595-3606
85. Shen, J., Herderick, E., Cornhill, J. F., Zsigmond, E., Kim, H. S., Kuhn, H., Guevara, N. V. and Chan, L. (1996) Macrophage-mediated 15-lipoxygenase expression protects against atherosclerosis development. J. Clin. Invest. 98, 2201-2208
86. Gronert, K., Maheshwari, N., Khan, N., Hassan, I. R., Dunn, M. and 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
87. Kronke, G., Katzenbeisser, J., Uderhardt, S., Zaiss, M. M., Scholtysek, C., Schabbauer, G., Zarbock, A., Koenders, M. I., Axmann, R., Zwerina, J. et al. (2009) 12/15-lipoxygenase counteracts inflammation and tissue damage in arthritis. J. Immunol. 183, 3383-3389
88. Leedom, A. J., Sullivan, A. B., Dong, B., Lau, D. and Gronert, K. (2010) Endogenous LXA4 circuits are determinants of pathological angiogenesis in response to chronic injury. Am. J. Pathol. 176, 74-84
89. Maddox, J. F. and Serhan, C. N. (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
90. Alessi, D. R., Caudwell, F. B., Andjelkovic, M., Hemmings, B. A. and Cohen, P. (1996) Molecular basis for the substrate specificity of protein kinase B; comparison with MAPKAP kinase-1 and p70 S6 kinase. FEBS Lett. 399, 333-338 (Pubitemid 26426877)
91. Ly, C., Arechiga, A. F., Melo, J. V., Walsh, C. M. and Ong, S. T. (2003) Bcr-Abl kinase modulates the translation regulators ribosomal protein S6 and 4E-BP1 in chronic myelogenous leukemia cells via the mammalian target of rapamycin. Cancer Res. 63, 5716-5722
92. Hong, S., Porter, T. F., Lu, Y., Oh, S. F., Pillai, P. S. and Serhan, C. N. (2008) Resolvin E1 metabolome in local inactivation during inflammation-resolution. J. Immunol. 180, 3512-3519
93. Rossi, A. G. and Sawatzky, D. A. (2008) The Resolution of Inflammation, Birkhäuser Verlag, Basel
94. Shimizu, T. (2009) Lipid mediators in health and disease: enzymes and receptors as therapeutic targets for the regulation of immunity and inflammation. Annu. Rev. Pharmacol. Toxicol. 49, 123-150
95. Iorio, M. V. and Croce, C. M. (2009) MicroRNAs in cancer: small molecules with a huge impact. J. Clin. Oncol. 27, 5848-5856
96. Lee, R. C., Feinbaum, R. L. and Ambros, V. (1993) The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75, 843-854 (Pubitemid 24014542)
97. Bartel, D. P. (2009) MicroRNAs: target recognition and regulatory functions. Cell 136, 215-233
98. Sheedy, F. J. and O'Neill, L. A. (2008) Adding fuel to fire: microRNAs as a new class of mediators of inflammation. Ann. Rheum. Dis. 67, iii50-55
99. Recchiuti, A., Krishnamoorthy, S., Fredman, G., Chiang, N. and Serhan, C. N. (2010) MicroRNAs in resolution of acute inflammation: identification of novel resolvin D1-miRNA circuits. FASEB J. 25, 544-560
100. Sun, Y. P., Oh, S. F., Uddin, J., Yang, R., Gotlinger, K., Campbell, E., Colgan, S. P., Petasis, N. A. and Serhan, C. N. (2007) Resolvin D1 and its aspirin-triggered 17R epimerStereochemical assignments, anti-inflammatory properties, and enzymatic inactivation. J. Biol. Chem. 282, 9323-9334
101. Sheedy, F. J., Palsson-McDermott, E., Hennessy, E. J., Martin, C., O'Leary, J. J., Ruan, Q., Johnson, D. S., Chen, Y. and O'Neill, L. A. (2009) Negative regulation of TLR4 via targeting of the proinflammatory tumor suppressor PDCD4 by the microRNA miR-21. Nat. Immunol. 11, 141-147
102. Burr, G. O. and Burr, M. M. (1929) A new deficiency disease produced by the rigid exclusion of fat from the diet. J. Biol. Chem. 82, 345-367
103. Takano, T., Clish, C. B., Gronert, K., Petasis, N. and Serhan, C. N. (1998) Neutrophil-mediated changes in vascular permeability are inhibited by topical application of aspirin-triggered 15-epi-lipoxin A4 and novel lipoxin B4 stable analogues. J. Clin. Invest. 101, 819-826
104. Clish, C. B., O'Brien, J. A., Gronert, K., Stahl, G. L., Petasis, N. A. and Serhan, C. N. (1999) Local and systemic delivery of a stable aspirin-triggered lipoxin prevents neutrophil recruitment in vivo. Proc. Natl. Acad. Sci. U.S.A. 96, 8247-8252
105. Serhan, C. N., Jain, A., Marleau, S., Clish, C., Kantarci, A., Behbehani, B., Colgan, S. P., Stahl, G. L., Merched, A., Petasis, N. A. et al. (2003) Reduced inflammation and tissue damage in transgenic rabbits overexpressing 15-lipoxygenase and endogenous anti-inflammatory lipid mediators. J. Immunol. 171, 6856-6865 (Pubitemid 37532121)
106. Gewirtz, A. T., Neish, A. S. and Madara, J. L. (2002) Mechanisms of active intestinal inflammation and potential down-regulation via lipoxins. Adv. Exp. Med. Biol. 507, 229-236
107. Levy, B. D., De Sanctis, G. T., Devchand, P. R., Kim, E., Ackerman, K., Schmidt, B. A., Szczeklik, W., Drazen, J. M. and Serhan, C. N. (2002) Multi-pronged inhibition of airway hyper-responsiveness and inflammation by lipoxin A(4). Nat. Med. 8, 1018-1023
108. Karp, C. L., Flick, L. M., Park, K. W., Softic, S., Greer, T. M., Keledjian, R., Yang, R., Uddin, J., Guggino, W. B., Atabani, S. F. et al. (2004) Defective lipoxin-mediated anti-inflammatory activity in the cystic fibrosis airway. Nat. Immunol. 5, 388-392
109. Chiang, N., Gronert, K., Clish, C. B., O'Brien, J. A., Freeman, M. W. and Serhan, C. N. (1999) Leukotriene B4 receptor transgenic mice reveal novel protective roles for lipoxins and aspirin-triggered lipoxins in reperfusion. J. Clin. Invest. 104, 309-316
110. Scalia, R., Gefen, J., Petasis, N. A., Serhan, C. N. and Lefer, A. M. (1997) Lipoxin A4 stable analogs inhibit leukocyte rolling and adherence in the rat mesenteric microvasculature: role of P-selectin. Proc. Natl. Acad. Sci. U.S.A. 94, 9967-9972
111. Fierro, I. M., Kutok, J. L. and Serhan, C. N. (2002) Novel lipid mediator regulators of endothelial cell proliferation and migration: aspirin-triggered-15R-lipoxin A(4) and lipoxin A(4). J. Pharmacol. Exp. Ther. 300, 385-392
112. Devchand, P. R., Schmidt, B. A., Primo, V. C., Zhang, Q. Y., Arnaout, M. A., Serhan, C. N. and Nikolic, B. (2005) A synthetic eicosanoid LX-mimetic unravels host-donor interactions in allogeneic BMT-induced GvHD to reveal an early protective role for host neutrophils. FASEB J. 19, 203-210
113. Papayianni, A., Serhan, C. N., Phillips, M. L., Rennke, H. G. and Brady, H. R. (1995) Transcellular biosynthesis of lipoxin A4 during adhesion of platelets and neutrophils in experimental immune complex glomerulonephritis. Kidney Int. 47, 1295-1302
114. Svensson, C. I., Zattoni, M. and Serhan, C. N. (2007) Lipoxins and aspirin-triggered lipoxin inhibit inflammatory pain processing. J. Exp. Med. 204, 245-252
115. Bandeira-Melo, C., Serra, M. F., Diaz, B. L., Cordeiro, R. S., Silva, P. M., Lenzi, H. L., Bakhle, Y. S., Serhan, C. N. and Martins, M. A. (2000) Cyclooxygenase-2-derived prostaglandin E2 and lipoxin A4 accelerate resolution of allergic edema in Angiostrongylus costaricensis-infected rats: relationship with concurrent eosinophilia. J. Immunol. 164, 1029-1036
116. Chen, Y., Hao, H., He, S., Cai, L., Li, Y., Hu, S., Ye, D., Hoidal, J., Wu, P. and Chen, X. (2010) Lipoxin A4 and its analogue suppress the tumor growth of transplanted H22 in mice: the role of antiangiogenesis. Mol. Cancer Ther. 9, 2164-2174
117. Levy, B. D., Zhang, Q. Y., Bonnans, C., Primo, V., Reilly, J. J., Perkins, D. L., Liang, Y., Amin Arnaout, M., Nikolic, B. and Serhan, C. N. (2011) The endogenous pro-resolving mediators lipoxin A4 and resolvin E1 preserve organ function in allograft rejection. Prostaglandins Leukotrienes Essent. Fatty Acids 84, 43-50
118. Conte, F. P., Menezes-de-Lima, Jr, O., Verri, Jr, W. A., Cunha, F. Q., Penido, C. and Henriques, M. G. (2010) Lipoxin A(4) attenuates zymosan-induced arthritis by modulating endothelin-1 and its effects. Br. J. Pharmacol. 161, 911-924
119. Zhou, M., Chen, B., Sun, H., Deng, Z., Andersson, R. and Zhang, Q. (2011) The protective effects of Lipoxin A(4) during the early phase of severe acute pancreatitis in ratsScand. J. Gastroenterol. 46, 211-219
120. Connor, K. M., SanGiovanni, J. P., Lofqvist, C., Aderman, C. M., Chen, J., Higuchi, A., Hong, S., Pravda, E. A., Majchrzak, S., Carper, D. et al. (2007) Increased dietary intake of omega-3-polyunsaturated fatty acids reduces pathological retinal angiogenesis. Nat. Med. 13, 868-873
121. Ishida, T., Yoshida, M., Arita, M., Nishitani, Y., Nishiumi, S., Masuda, A., Mizuno, S., Takagawa, T., Morita, Y., Kutsumi, Y. et al. (2010) Resolvin E1, an endogenous lipid derived from eicosapentaenoic acid, prevents dextran sulfate sodium-induced colitis. Inflammatory Bowel Dis. 16, 87-95
122. Haworth, O., Cernadas, M., Yang, R., Serhan, C. N. and Levy, B. D. (2008) Resolvin E1 regulates interleukin 23, interferon-gamma and lipoxin A4 to promote the resolution of allergic airway inflammation. Nat. Immunol. 9, 873-879
123. Aoki, H., Hisada, T., Ishizuka, T., Utsugi, M., Ono, A., Koga, Y., Sunaga, N., Nakakura, T., Okajima, F., Dobashi, K. and Mori, M. (2010) Protective effect of resolvin E1 on the development of asthmatic airway inflammation. Biochem. Biophys. Res. Commun. 400, 128-133
124. Aoki, H., Hisada, T., Ishizuka, T., Utsugi, M., Kawata, T., Shimizu, Y., Okajima, F., Dobashi, K. and Mori, M. (2008) Resolvin E1 dampens airway inflammation and hyperresponsiveness in a murine model of asthma. Biochem. Biophys. Res. Commun. 367, 509-515
125. González-Périz, A., Horrillo, R., Ferré, N., Gronert, K., Dong, B., Morán-Salvador, E., Titos, E., Martínez-Clemente, M., López-Parra, M., Arroyo, V. and Clària, J. (2009) Obesity-induced insulin resistance and hepatic steatosis are alleviated by omega-3 fatty acids: a role for resolvins and protectins. FASEB J. 23, 1946-1957
126. Xu, Z.-Z., Zhang, L., Liu, T., Park, J.-Y., Berta, T., Yang, R., Serhan, C. N. and Ji, R.-R. (2010) Resolvins RvE1 and RvD1 attenuate inflammatory pain via central and peripheral actions. Nat. Med. 16, 592-597
127. Keyes, K. T., Ye, Y., Lin, Y., Zhang, C., Perez-Polo, J. R., Gjorstrup, P. and Birnbaum, Y. (2010) Resolvin E1 protects the rat heart against reperfusion injury. Am. J. Physiol. Heart Circ. Physiol. 299, H153-H164
128. Rajasagi, N. K., Reddy, P. B., Suryawanshi, A., Mulik, S., Gjorstrup, P. and Rouse, B. T. (2011) Controlling herpes simplex virus-induced ocular inflammatory lesions with the lipid-derived mediator resolvin e1. J. Immunol. 186, 1735-1746
129. Duffield, J. S., Hong, S., Vaidya, V. S., Lu, Y., Fredman, G., Serhan, C. N. and Bonventre, J. V. (2006) Resolvin D series and protectin D1 mitigate acute kidney injury. J. Immunol. 177, 5902-5911
130. Huang, L., Wang, C.-F., Serhan, C. N. and Strichartz, G. (2011) Enduring prevention and transient reduction of post-operative pain by intrathecal resolvin D1. Pain 152, 557-565
131. Ariel, A., Li, P. L., Wang, W., Tang, W. X., Fredman, G., Hong, S., Gotlinger, K. H. and Serhan, C. N. (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
132. Levy, B. D., Kohli, P., Gotlinger, K., Haworth, O., Hong, S., Kazani, S., Israel, E., Haley, K. J. and Serhan, C. N. (2007) Protectin D1 is generated in asthma and dampens airway inflammation and hyperresponsiveness. J. Immunol. 178, 496-502
133. Marcheselli, V. L., Hong, S., Lukiw, W. J., Tian, X. H., Gronert, K., Musto, A., Hardy, M., Gimenez, J. M., Chiang, N., Serhan, C. N. and Bazan, N. G. (2003) Novel docosanoids inhibit brain ischemia - reperfusion-mediated leukocyte infiltration and pro-inflammatory gene expression. J. Biol. Chem. 278, 43807-43817
134. Zhao, Y., Calon, F., Julien, C., Winkler, J. W., Petasis, N. A., Lukiw, W. J. and Bazan, N. G. (2011) Docosahexaenoic acid-derived neuroprotectin D1 induces neuronal survival via secretase and PPARgamma-mediated mechanisms in Alzheimer's disease models. PLoS ONE 6, e15816
135. Spite, M., Norling, L. V., Summers, L., Yang, R., Cooper, D., Petasis, N. A., Flower, R. J., Perretti, M. and Serhan, C. N. (2009) Resolvin D2 is a potent regulator of leukocytes and controls microbial sepsis. Nature 461, 1287-1291
136. Serhan, C. N., Yang, R., Martinod, K., Kasuga, K., Pillai, P. S., Porter, T. F., Oh, S. F. and Spite, M. (2009) Maresins: novel macrophage mediators with potent antiinflammatory and proresolving actions. J. Exp. Med. 206, 15-23