These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Lipopolysaccharide triggered TNF-alpha-induced hepatocyte apoptosis in a murine non-alcoholic steatohepatitis model.
    Author: Kudo H, Takahara T, Yata Y, Kawai K, Zhang W, Sugiyama T.
    Journal: J Hepatol; 2009 Jul; 51(1):168-75. PubMed ID: 19446916.
    Abstract:
    BACKGROUND/AIMS: Endogenous gut-derived bacterial endotoxins have been implicated as an important cofactor in the pathogenesis of liver injury, although their contribution to the progression of non-alcoholic steatohepatitis (NASH) remains unclear. METHODS: Male C57BL/6 mice were fed a methionine-choline-deficient (MCD) diet or a standard diet for 17 days, following which they were injected with lipopolysaccharide (LPS) intraperitoneally and sacrificed after 6h. In an in vitro experiment, RAW264.7 cells, a mouse macrophage cell line, and primary mouse hepatocytes were co-treated with hydrogen peroxide (H(2)O(2)) and LPS or tumour necrosis factor (TNF)-alpha. RESULTS: Compared to the control mice, LPS treatment significantly increased hepatic TNF-alpha production in MCD mice. LPS also significantly increased TUNEL-positive cells, which were especially observed in the perivenular area. The apoptotic change was inhibited by co-treatment with a neutralizing anti-mouse TNF receptor antibody or pentoxifylline. In an in vitro experiment, treatment with H(2)O(2) synergistically enhanced LPS-induced TNF-alpha production in RAW264.7 cells, accompanied by an up-regulation of CD14 mRNA. Moreover, co-treatment with TNF-alpha- and H(2)O(2)-induced apoptosis in primary hepatocytes, although neither TNF-alpha nor H(2)O(2) could do so independently. CONCLUSIONS: LPS up-regulated TNF-alpha production, which induced hepatocyte apoptosis in a murine NASH model. LPS may play a key role in the pathogenesis of NASH.
    [Abstract] [Full Text] [Related] [New Search]