Antagonizing arachidonic acid-derived eicosanoids reduces inflammatory Th17 and Th1 cell-mediated inflammation and colitis severity.
Antagonizing arachidonic acid-derived eicosanoids reduces inflammatory Th17 and Th1 cell-mediated inflammation and colitis severity.
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DOI：
10.1155/2014/917149
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发表时间：
2014
影响因子：
4.6
通讯作者：
Chapkin RS
中科院分区：
文献类型：
--
作者：
Monk JM;Turk HF;Fan YY;Callaway E;Weeks B;Yang P;McMurray DN;Chapkin RS
在结肠炎期间，两种炎症 T 细胞亚群 Th17 和 Th1 细胞的激活会促进持续的肠道炎症反应。 n-6 多不饱和脂肪酸 (PUFA) 衍生的类二十烷酸，例如前列腺素 E2 (PGE2)，可促进 Th17 细胞介导的炎症，而 n-3 PUFA 拮抗 Th17 和 Th1 细胞并抑制 PGE2 水平。我们利用两种不同地拮抗 PGE2 水平的基因小鼠模型来检查对 Th17 细胞的影响以及三硝基苯磺酸 (TNBS) 诱导的结肠炎的疾病结果。 Fat-1 小鼠含有来自秀丽隐杆线虫的 ω3 去饱和酶基因，可从头合成 n-3 PUFA，从而减少 n-6 PUFA 衍生的类二十烷酸的生物合成。相比之下，Fads1 Null 小鼠含有被破坏的 Δ5 去饱和酶基因，并产生较低水平的 n-6 PUFA 衍生的类二十烷酸。与Wt同窝小鼠相比，Fat-1和Fads1 Null小鼠表现出相似的结肠炎表型，其特征是结肠粘膜炎症类二十烷酸水平和Th17细胞标志物（IL-17A、RORγτ和IL-23）的mRNA表达降低、Th17细胞百分比降低以及结肠损伤评分改善（P≤0.05）。因此，在结肠炎期间，在两种遗传上不同的模型中获得了相似的结果，这两种模型都通过不同的机制拮抗 PGE2 水平。我们的数据强调了 n-6 PUFA 衍生的类二十烷酸在促进 Th17 细胞介导的结肠炎症方面的关键影响。
During colitis, activation of two inflammatory T cell subsets, Th17 and Th1 cells, promotes ongoing intestinal inflammatory responses. n-6 polyunsaturated fatty acid- (PUFA-) derived eicosanoids, such as prostaglandin E2 (PGE2), promote Th17 cell-mediated inflammation, while n-3 PUFA antagonize both Th17 and Th1 cells and suppress PGE2 levels. We utilized two genetic mouse models, which differentially antagonize PGE2 levels, to examine the effect on Th17 cells and disease outcomes in trinitrobenzene sulfonic acid- (TNBS-) induced colitis. Fat-1 mice contain the ω3 desaturase gene from C. elegans and synthesize n-3 PUFA de novo, thereby reducing the biosynthesis of n-6 PUFA-derived eicosanoids. In contrast, Fads1 Null mice contain a disrupted Δ5 desaturase gene and produce lower levels of n-6 PUFA-derived eicosanoids. Compared to Wt littermates, Fat-1 and Fads1 Null mice exhibited a similar colitic phenotype characterized by reduced colonic mucosal inflammatory eicosanoid levels and mRNA expression of Th17 cell markers (IL-17A, RORγτ, and IL-23), decreased percentages of Th17 cells and, improved colon injury scores (P ≤ 0.05). Thus, during colitis, similar outcomes were obtained in two genetically distinct models, both of which antagonize PGE2 levels via different mechanisms. Our data highlight the critical impact of n-6 PUFA-derived eicosanoids in the promotion of Th17 cell-mediated colonic inflammation.
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人白细胞介素17产生的细胞起源于CD161+ CD4+ T细胞前体。
影响因子：
15.3
作者：
Cosmi, Lorenzo;De Palma, Raffaele;Santarlasci, Veronica;Maggi, Laura;Capone, Manuela;Frosali, Francesca;Rodolico, Gabriella;Querci, Valentina;Abbate, Gianfranco;Angeli, Roberta;Berrino, Liberato;Fambrini, Massimiliano;Caproni, Marzia;Tonelli, Francesco;Lazzeri, Elena;Parronchi, Paola;Liotta, Francesco;Maggi, Enrico;Romagnani, Sergio;Annunziato, Francesco
通讯作者：
Annunziato, Francesco
影响因子：
20.3
作者：
Chizzolini, Carlo;Chicheportiche, Rachel;Dayer, Jean-Michel
通讯作者：
Dayer, Jean-Michel
影响因子：
7.1
作者：
Caughey, GE;Mantzioris, E;James, MJ
通讯作者：
James, MJ
影响因子：
6.5
作者：
Fan, Yang-Yi;Monk, Jennifer M.;Chapkin, Robert S.
通讯作者：
Chapkin, Robert S.
影响因子：
3.2
作者：
Hirata, I;Murano, M;Katsu, K
通讯作者：
Katsu, K