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Deletion of caveolin-1 attenuates LPS/GalN-induced acute liver injury in mice.


ABSTRACT: 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 (TLR4) and CD14 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-?B (NF-?B) 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-CD14-TLR4-NF-?b pathway and alleviated acute liver injury in mice.

SUBMITTER: Tsai TH 

PROVIDER: S-EPMC6201225 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Deletion of caveolin-1 attenuates LPS/GalN-induced acute liver injury in mice.

Tsai Tsung-Huang TH   Tam Kabik K   Chen Shu-Fen SF   Liou Jun-Yang JY   Tsai Yi-Chen YC   Lee Yen-Ming YM   Huang Tai-Yu TY   Shyue Song-Kun SK  

Journal of cellular and molecular medicine 20180822 11


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<sup>-/-</sup> ) mice. Hepatic Cav-1 expression was induced post-LPS/GalN treatment in wild-type mice. LPS/GalN-treated Cav-1<sup>-/-</sup> mice showed reduced lethality and markedly attenuated liver damage, neutrophil infiltration an  ...[more]

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