IL-33 protects murine viral fulminant hepatitis by targeting coagulation hallmark protein FGL2/fibroleukin expression. (July 2017)

• Record Type: Journal Article
• Authors: Yu, Haijing; Liu, Yang; Huang, Jiaquan; Wang, Hongwu; Yan, Weiming; Xi, Dong; Shen, Guanxin; Luo, Xiaoping; Ning, Qin
• Is Part Of: Molecular immunology. Volume 87(2017:Jul.)
• Page Start: 171
• Page End: 179
• Publication Date: 2017-07
• Subjects: FH fulminant hepatitis -- MHV-3 murine hepatitis virus strain 3 -- FGL2 Fibrinogen-like protein 2 -- ST2 IL-1 receptor-like 1 -- ALF acute liver failure -- PFU plaque-forming units -- PBS phosphate-buffered saline -- ALT alanine aminotransferase -- AST aspartate aminotransferase -- PCA pro-coagulant activity -- HRP horseradish peroxidase -- TUNEL terminal deoxynucleotidyl transferase dUTP nick end labeling; IL-33 -- FGL2 -- Hepatitis -- MHV-3 -- Pro-coagulant activity -- Macrophage; Immunochemistry -- Periodicals; Molecular biology -- Periodicals; Immunochemistry -- Periodicals; Allergy and Immunology -- Periodicals; Molecular Biology -- Periodicals; Immunochimie -- Périodiques; Biologie moléculaire -- Périodiques; Immunochemistry; Molecular biology; Periodicals; Electronic journals; 571.96
• DOI: 10.1016/j.molimm.2017.04.011
• Languages: English
• ISSNs: 0161-5890

Abstract

Highlights: MHV-3 infection causes IL-33 levels increasing and developing of fulminant hepatitis. IL-33 treatment leads to attenuation of the disease and remarkable reduction of FGL2. In vitro IL-33 administration prevents FGL2 secretion by macrophages. IL-33 had marked effects on treating viral fulminant hepatitis by targeting FGL2. Abstract: 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.