Deletion of caveolin-1 attenuates LPS/GalN-induced acute liver injury in mice.
J Cell Mol Med
; 22(11): 5573-5582, 2018 11.
Article
in En
| MEDLINE
| ID: mdl-30134043
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-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-CD14-TLR4-NF-κb pathway and alleviated acute liver injury in mice.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Caveolin 1
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Chemical and Drug Induced Liver Injury
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Inflammation
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Liver
Limits:
Animals
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Humans
Language:
En
Year:
2018
Type:
Article