title: Maresin 1, a proresolving lipid mediator derived from omega-3 polyunsaturated fatty acids, exerts protective actions in murine models of colitis.
abstract: It has been previously reported that dietary fish oils, which are rich in the polyunsaturated fatty acids eicosapentaenoic acid and docosahexaenoic acid, can exert beneficial effects in inflammatory bowel disease. In this study, we investigated the effects of docosahexaenoic acid-derived lipid mediator maresin 1 (MaR1) in dextran sulfate sodium (DSS)- and 2,4,6-trinitrobenzenesulfonic acid-induced colitis in mice. Systemic treatment with MaR1 significantly attenuated both DSS- and 2,4,6-trinitrobenzene sulfonic acid-induced colonic inflammation by improving the disease activity index and reducing body weight loss and colonic tissue damage. MaR1 treatment also induced a significant decrease in levels of inflammatory mediators, such as IL-1β, TNF-α, IL-6, and IFN-γ, in the acute protocol, as well as IL-1β and IL-6, but not TNF-α and INF-γ, in the chronic DSS colitis protocol. Additionally, MaR1 decreased ICAM-1 mRNA expression in both the acute and chronic protocols of DSS-induced colitis. Furthermore, the beneficial effects of MaR1 seem to be associated with inhibition of the NF-κB pathway. Moreover, incubation of LPS-stimulated bone marrow-derived macrophage cultures with MaR1 reduced neutrophil migration and reactive oxygen species production, besides decreasing IL-1β, TNF-α, IL-6, and INF-γ production. Interestingly, macrophages incubated only with MaR1 showed a significant upregulation of mannose receptor C, type 1 mRNA expression, an M2 macrophage phenotype marker. These results indicate that MaR1 consistently protects mice against different models of experimental colitis, possibly by inhibiting the NF-κB pathway and consequently multiple inflammatory mediators, as well as by enhancing the macrophage M2 phenotype.
authors.affiliation: Department of Pharmacology, Federal University of Santa Catarina, Florianópolis, Santa Catarina 88049-900, Brazil.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Marcon
authors.forename: Allisson F
authors.initials: AF
authors.lastname: Bento
authors.forename: Rafael C
authors.initials: RC
authors.lastname: Dutra
authors.forename: Maira A
authors.initials: MA
authors.lastname: Bicca
authors.forename: Daniela F P
authors.initials: DF
authors.lastname: Leite
authors.forename: João B
authors.initials: JB
authors.lastname: Calixto
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy*; D003106:Colon / Q000187:drug effects / Q000473:pathology; D016264:Dextran Sulfate; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D007371:Interferon-gamma / Q000096:biosynthesis; D053583:Interleukin-1beta / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D017382:Reactive Oxygen Species / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics; D011971:Receptors, Immunologic; D014302:Trinitrobenzenesulfonic Acid; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: C535211:7,14-dihydroxydocosa-4,8,10,12,16,19-hexaenoic acid; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; C581013:MRC1 protein, mouse; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D004281:Docosahexaenoic Acids; D007371:Interferon-gamma; D014302:Trinitrobenzenesulfonic Acid; D016264:Dextran Sulfate