Open AccessDeletion of caveolin‐1 attenuates LPS /GalN‐induced acute liver injury in mice
Author(s) -
Tsai TsungHuang,
Tam Kabik,
Chen ShuFen,
Liou JunYang,
Tsai YiChen,
Lee YenMing,
Huang TaiYu,
Shyue SongKun
Publication year - 2018
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13831
Subject(s) - lipopolysaccharide , liver injury , chemokine , nitric oxide , apoptosis , nitric oxide synthase , chemistry , inflammation , cell adhesion molecule , biology , immunology , pharmacology , endocrinology , biochemistry
Acute hepatic injury caused by inflammatory liver disease is associated with high mortality. This study examined the role of caveolin‐1 (Cav‐1) in lipopolysaccharide ( LPS ) and D‐galactosamine (GalN)‐induced fulminant hepatic injury in wild type and Cav‐1‐null (Cav‐1 −/− ) mice. Hepatic Cav‐1 expression was induced post‐ LPS /GalN treatment in wild‐type mice. LPS /GalN‐treated Cav‐1 −/− mice showed reduced lethality and markedly attenuated liver damage, neutrophil infiltration and hepatocyte apoptosis as compared to wild‐type mice. Cav‐1 deletion significantly reduced LPS /GalN‐induced caspase‐3, caspase‐8 and caspase‐9 activation and pro‐inflammatory cytokine and chemokine expression. Additionally, Cav‐1 −/− mice showed suppressed expression of Toll‐like receptor 4 ( TLR 4) and CD 14 in Kupffer cells and reduced expression of vascular cell adhesion molecule 1 and intercellular adhesion molecule 1 in liver cells. Cav‐1 deletion impeded LPS /GalN‐induced inducible nitric oxide synthase expression and nitric oxide production and hindered nuclear factor‐κB ( NF ‐κB) activation. Taken together, Cav‐1 regulated the expression of mediators that govern LPS ‐induced inflammatory signalling in mouse liver. Thus, deletion of Cav‐1 suppressed the inflammatory response mediated by the LPS ‐ CD 14‐ TLR 4‐ NF ‐κb pathway and alleviated acute liver injury in mice.