Maresin 1, a Proresolving Lipid Mediator Derived from Omega-3 Polyunsaturated Fatty Acids, Exerts Protective Actions in Murine Models of Colitis
Maresin 1, a Proresolving Lipid Mediator Derived from Omega-3 Polyunsaturated Fatty Acids, Exerts Protective Actions in Murine Models of Colitis
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DOI：
10.4049/jimmunol.1202743
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发表时间：
2013-10-15
影响因子：
4.4
通讯作者：
Calixto, Joao B.
中科院分区：
文献类型：
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作者：
Marcon, Rodrigo;Bento, Allisson F.;Calixto, Joao B.
此前有报道称，富含多不饱和脂肪酸二十碳五烯酸和二十二碳六烯酸的膳食鱼油对炎症性肠病有有益作用。在这项研究中，我们研究了二十二碳六烯酸衍生的脂质介质marsin 1 （MaR1）在葡聚糖硫酸钠(DSS)-和2,4,6-三硝基苯磺酸诱导的小鼠结肠炎中的作用。全身使用MaR1治疗可通过改善疾病活动性指数、减轻体重减轻和结肠组织损伤，显著减轻DSS-和2,4,6-三硝基苯磺酸诱导的结肠炎症。在急性方案中，MaR1治疗还诱导炎症介质水平的显著降低，如IL-1 β， tnf - α， IL-6和ifn - γ，以及IL-1 β和IL-6，但在慢性DSS结肠炎方案中，没有tnf - α和inf - γ。此外，在dss诱导的急性和慢性结肠炎中，MaR1均可降低ICAM-1 mRNA的表达。此外，MaR1的有益作用似乎与nf - κ B通路的抑制有关。此外，在lps刺激的骨髓源性巨噬细胞培养物中加入MaR1，除了降低IL-1 β、tnf - α、IL-6和inf - γ的产生外，还能减少中性粒细胞的迁移和活性氧的产生。有趣的是，仅用MaR1孵养的巨噬细胞显示M2巨噬细胞表型标志物甘露糖受体C（1型mRNA）表达显著上调。这些结果表明，MaR1一致地保护小鼠免受不同模型的实验性结肠炎，可能是通过抑制NF-kappa B途径，从而抑制多种炎症介质，以及通过增强巨噬细胞M2表型。
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-1 beta, TNF-alpha, IL-6, and IFN-gamma, in the acute protocol, as well as IL-1 beta and IL-6, but not TNF-alpha and INF-gamma, 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-kappa B pathway. Moreover, incubation of LPS-stimulated bone marrow-derived macrophage cultures with MaR1 reduced neutrophil migration and reactive oxygen species production, besides decreasing IL-1 beta, TNF-alpha, IL-6, and INF-gamma 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-kappa B pathway and consequently multiple inflammatory mediators, as well as by enhancing the macrophage M2 phenotype.