LPS-induced inflammation desensitizes hepatocytes to Fas-induced apoptosis through Stat3 activation-The effect can be reversed by ruxolitinib.

ABSTRACT: Recent studies have established a concept of tumour necrosis factor-α (TNF-α)/Fas signalling crosstalk, highlighting TNF-α as a critical cytokine in sensitizing hepatocytes to death induced by Fas activation. However, in the exact inflammatory response, besides TNF-α, many other mediators, that might modulate apoptotic response differentially, are released. To resolve the issue, we studied the effects of lipopolysaccharide (LPS), one of the crucial inductors of inflammation in the liver, on apoptotic outcome. We show that LPS-induced inflammation diminishes the sensitivity of hepatocytes to Fas stimulus in vivo at caspase-8 level. Analysis of molecular mechanisms revealed an increased expression of various pro-inflammatory cytokines in non-parenchymal liver cells and hepatocyte-specific in

SUBMITTER: Markotic A 

PROVIDER: S-EPMC7077556 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature