Journal
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
Volume 22, Issue 11, Pages 5573-5582Publisher
WILEY
DOI: 10.1111/jcmm.13831
Keywords
acute liver injury; caveolin-1; D-galactosamine; lipopolysaccharide; toll-like receptor 4
Categories
Funding
- Institute of Biomedical Sciences, Academia Sinica [CRC104-P04]
- Ministry of Science and Technology [NSC 99-2628-B-001-013-MY3, MOST106-2321-B-001-014]
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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.
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