IL‐33 protects murine viral fulminant hepatitis by targeting coagulation hallmark protein FGL2/fibroleukin expression
IL‐33 protects murine viral fulminant hepatitis by targeting coagulation hallmark protein FGL2/fibroleukin expression
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DOI：
10.1016/j.molimm.2017.04.011
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发表时间：
2017-07
影响因子：
3.6
通讯作者：
Hai-jing Yu;Yang Liu;Jiaquan Huang;Hongwu Wang;Weiming Yan;D. Xi;G. Shen;Xiaoping Luo;Q. Ning
中科院分区：
文献类型：
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作者：
Hai-jing Yu;Yang Liu;Jiaquan Huang;Hongwu Wang;Weiming Yan;D. Xi;G. Shen;Xiaoping Luo;Q. Ning
暴发性肝炎（FH）的特点是肝功能衰竭快，死亡率高。病毒性FH的发病机制包括病毒诱导的免疫激活、炎症以及随后的肝细胞凋亡和坏死。然而，FH进展的机制尚不清楚。IL-33是IL-1相关细胞因子的一员，被认为是参与多种疾病的“alarmin”，但其在FH凝血中的确切作用尚不十分清楚。在我们的研究中，我们发现IL-33在感染小鼠肝炎病毒株3（MHV-3）的小鼠中显著升高。这伴随着肝脏中促凝血纤维蛋白原样蛋白2（FGL 2）的增加。先前的研究表明，FGL 2的增加是FH和肝坏死的诊断，并且没有FGL 2的动物在FH期间具有更好的存活率。我们的研究表明，在MHV-3感染中给予IL-33可促进FH期间的存活，并显著降低FGL 2表达和肝脏炎症。体外IL-33处理分别消除了MHV-3和IFN-γ诱导的RAW 264.7和THP-1细胞中的FGL 2表达。总之，我们的研究表明，IL-33通过拮抗促凝血蛋白FGL 2的表达来保护小鼠免受病毒性暴发性肝炎的侵害。
Fulminant hepatitis (FH) is characterized by rapid liver failure and high mortality. The pathogenesis of viral FH includes virus-induced immune activation, inflammation, and subsequent hepatic apoptosis and necrosis. However, the mechanisms that underlie FH progression are unclear. IL-33 is a member of the IL-1-related cytokines, considered to be an “alarmin” that participates in various diseases, but its precise role in the coagulation of FH is not very clear. In our study, we found that IL-33 is significantly elevated in mice infected with murine hepatitis virus strain 3 (MHV-3). This is accompanied by an increase in pro-coagulant fibrinogen-like protein 2 (FGL2) in the liver. Previous studies have suggested that an increase in FGL2 is diagnostic of FH and liver necrosis, and animals with no FGL2 had better survivorship during FH. Our studies showed that IL-33 administration in a MHV-3 infection promoted survival during FH, with a significant reduction in FGL2 expression and liver inflammation. In vitro IL-33 treatment abrogated MHV-3 and IFN-γ induced FGL2 expression in RAW264.7 and THP-1 cells, respectively. In conclusion, our research suggests that IL-33 protects against viral fulminant hepatitis in mice by antagonizing expression of the pro-coagulant protein FGL2.