Endogenous n-3 Polyunsaturated Fatty Acids Attenuate T Cell-Mediated Hepatitis via Autophagy Activation.
Endogenous n-3 Polyunsaturated Fatty Acids Attenuate T Cell-Mediated Hepatitis via Autophagy Activation.
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内源性 n-3 多不饱和脂肪酸通过自噬激活减轻 T 细胞介导的肝炎
DOI：
10.3389/fimmu.2016.00350
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发表时间：
2016
影响因子：
7.3
通讯作者：
Zuo D
中科院分区：
文献类型：
--
作者：
Li Y;Tang Y;Wang S;Zhou J;Zhou J;Lu X;Bai X;Wang XY;Chen Z;Zuo D
ω-3多不饱和脂肪酸（n-3 PUFA）在几种肝脏疾病中发挥抗炎作用，包括肝硬化、急性肝衰竭和脂肪肝。迄今为止，对它们在免疫介导的肝脏疾病中的作用知之甚少。在这项研究中，我们使用富含内源性n-3 PUFAs的fat-1转基因小鼠来研究n-3 PUFAs在免疫介导的肝损伤中的作用。将伴刀豆球蛋白A（Con A）静脉内给予野生型（WT）和fat-1转基因小鼠以诱导T细胞介导的肝炎。在Con A给药的fat-1转基因小鼠中显示出降低的肝损伤，如通过降低的死亡率、减弱的肝坏死、降低的血清丙氨酸氨基转移酶活性和抑制促炎细胞因子（例如，TNF-α、IL-6、IL-17 A和IFN-γ）。体内和体外研究表明，n-3 PUFAs显着抑制ConA刺激后肝T细胞的活化和Th 1细胞的分化。进一步的研究表明，与WT对应物相比，n-3 PUFA显着增加Con A处理的fat-1 T细胞中的自噬水平。用氯喹阻断肝脏自噬活性减少了Con A注射WT和fat-1转基因小鼠之间T细胞活化和肝损伤的差异。我们的结论是，n-3多不饱和脂肪酸限制刀豆蛋白A诱导的肝炎通过自噬依赖的机制，可作为一种新的治疗方法，自身免疫性肝炎。
Omega-3 polyunsaturated fatty acids (n-3 PUFAs) exert anti-inflammatory effects in several liver disorders, including cirrhosis, acute liver failure, and fatty liver disease. To date, little is known about their role in immune-mediated liver diseases. In this study, we used fat-1 transgenic mice rich in endogenous n-3 PUFAs to examine the role of n-3 PUFAs in immune-mediated liver injury. Concanavalin A (Con A) was administered intravenously to wild-type (WT) and fat-1 transgenic mice to induce T cell-mediated hepatitis. Reduced liver damage was shown in Con A-administrated fat-1 transgenic mice, as evidenced by decreased mortality, attenuated hepatic necrosis, lessened serum alanine aminotransferase activity, and inhibited production of pro-inflammatory cytokines (e.g., TNF-α, IL-6, IL-17A, and IFN-γ). In vivo and in vitro studies demonstrated that n-3 PUFAs significantly inhibited the activation of hepatic T cells and the differentiation of Th1 cells after Con A challenge. Further studies showed that n-3 PUFAs markedly increased autophagy level in Con A-treated fat-1 T cells compared with the WT counterparts. Blocking hepatic autophagy activity with chloroquine diminished the differences in T cell activation and liver injury between Con A-injected WT and fat-1 transgenic mice. We conclude that n-3 PUFAs limit Con A-induced hepatitis via an autophagy-dependent mechanism and could be exploited as a new therapeutic approach for autoimmune hepatitis.
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影响因子：
--
作者：
Cursio R;Colosetti P;Codogno P;Cuervo AM;Shen HM
通讯作者：
Shen HM
影响因子：
7.1
作者：
Calder, Philip C.
通讯作者：
Calder, Philip C.
影响因子：
13.6
作者：
Ichiki, Y;Aoki, CA;Gershwin, ME
通讯作者：
Gershwin, ME
影响因子：
4.4
作者：
Marcon, Rodrigo;Bento, Allisson F.;Calixto, Joao B.
通讯作者：
Calixto, Joao B.
影响因子：
7.2
作者：
Gerondakis, Steve;Siebenlist, Ulrich
通讯作者：
Siebenlist, Ulrich