ArticleJournal of cellular and molecular medicine2020
LPS-induced inflammation desensitizes hepatocytes to Fas-induced apoptosis through Stat3 activation-The effect can be reversed by ruxolitinib.
Article in Journal of cellular and molecular medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 15 citations in OpenAlex.
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- Modulation of Notch signaling pathway in activated hepatic stellate cells does not ameliorate the outcome of liver fibrosis in carbon tetrachloride and DDC-feeding models.Frontiers in pharmacology · 2024Article
- Citral-Enriched Fraction of Lemon Essential Oil Mitigates LPS-Induced Hepatocyte Injuries.Biology · 2023Article
- Lobeglitazone inhibits LPS-induced NLRP3 inflammasome activation and inflammation in the liver.PloS one · 2023Article
- Commensal gut microbiota-based strategies for oral delivery of therapeutic proteins.Trends in pharmacological sciences · 2022Review
- Tamoxifen Ameliorates Cholestatic Liver Fibrosis in Mice: Upregulation of TGFβ and IL6 Is a Potential Protective Mechanism.Biomedicines · 2022Article
- Elucidation of the Hdac2/Sp1/Molecular therapy. Nucleic acids · 2021Article
- Janus Kinase Inhibition Ameliorates Ischemic Stroke Injury and Neuroinflammation Through Reducing NLRP3 Inflammasome ActivationFrontiers in immunology · 2021Article
- FasL (rs763110) gene polymorphism is not associated with susceptibility to rheumatoid arthritis in Croatian population.Croatian medical journal · 2020Article
- Deficiency of interleukin-19 exacerbates lipopolysaccharide/D-galactosamine-induced acute liver failure.The Journal of veterinary medical science · 2020Article
- LPS-induced inflammation desensitizes hepatocytes to Fas-induced apoptosis through Stat3 activation-The effect can be reversed by ruxolitinib.Journal of cellular and molecular medicine · 2020Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
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 increase in Bcl-xL, associated with signal transducer and activator of transcription 3 (Stat3) phosphorylation. Pre-treatment with ruxolitinib, a selective Janus kinase (JAK) 1/2 inhibitor, prevented the LPS-induced Stat3 phosphorylation and restored the sensitivity of hepatocytes to Fas-mediated apoptosis. Furthermore, ruxolitinib pre-treatment diminished the LPS-induced Bcl-xL up-regulation without an inhibitory effect on LPS-induced expression of pro-inflammatory cytokines. In summary, although the reports are showing that the effects of isolated pro-inflammatory mediators, such as TNF-α or neutrophils, are pro-apoptotic, the overall effect of inflammatory milieu on hepatocytes in vivo is Stat3-dependent desensitization to Fas-mediated apoptosis.
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