Toll-like receptor-4 signaling and Kupffer cells play pivotal roles in the pathogenesis of non-alcoholic steatohepatitis

摘要: Background/Aims Studies in animal models and humans suggest a link between endotoxemia non-alcoholic steatohepatitis. Since Kupffer cells are responsible for clearing endotoxin activated via interaction with Toll-like receptor 4 (TLR-4), we examined the relationship hepatic TLR-4 expression cell content during genesis of Methods Male C57BL/6, C3H/HouJ mutant C3H/HeJ mice were fed control or methionine/choline-deficient diet (MCDD). In one group C57BL/6 mice, depleted by weekly intraperitoneal injections clodronate liposomes. After 3 weeks, serum ALT activity portal levels measured. Real-time PCR was used to examine mRNA TLR-4, TLR-2, CD14, MD-2, TGFβ, TNFα, CD36, PPAR-α, liver fatty acid binding protein (L-FABP) collagen α1. Results We observed histological evidence typical steatohepatitis, enhanced wild type MCDD. contrast, injury lipid accumulation markers significantly lower mice. Destruction liposomes blunted steatohepatitis prevented increases expression. Conclusions These findings demonstrate importance signaling underscore direct pathogenesis