ArticleHepatology (Baltimore, Md.)2006
Bile acids and cytokines inhibit the human cholesterol 7 alpha-hydroxylase gene via the JNK/c-jun pathway in human liver cells.
Article in Hepatology (Baltimore, Md.), 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
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Who cites it
88 citing papers in PubMed.
- Bioartificial Therapy of Sepsis: Changes of Norepinephrine-Dosage in Patients and Influence on Dynamic and Cell Based Liver Tests during Extracorporeal Treatments.BioMed research international · 2016Trial
- Brain control of hepatic bile acid homeostasis through Bdnf exon I-positive neurons in the paraventricular hypothalamus.Nature communications · 2026Article
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- Disentangling Organ-Specific Roles of Farnesoid X Receptor in Bile Acid and Glucolipid Metabolism.Liver international : official journal of the International Association for the Study of the Liver · 2025Article
- Hypercholesterolemia and inflammation-Cooperative cardiovascular risk factors.European journal of clinical investigation · 2025Review
- Dysregulated bile acid metabolism as a novel player in gout progression: emerging therapeutic strategies.Frontiers in endocrinology · 2025Review
- Impacts of liver macrophages, gut microbiota, and bile acid metabolism on the differences in iHFC diet-induced MASH progression between TSNO and TSOD mice.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Article
- Osteocytes/Osteoblasts Produce SAA3 to Regulate Hepatic Metabolism of Cholesterol.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Assessment of Two Potential Probiotic Strains As Anti-Obesity Supplements Under High-Fat Feeding Conditions.Probiotics and antimicrobial proteins · 2023Article
- FXR Friend-ChIPs in the Enterohepatic System.Seminars in liver disease · 2023Review
- Perinatal exposure to UDCA prevents neonatal cholestasis in Cyp2c70Pediatric research · 2023Article
- Interleukin-1ß Attenuates Expression of Augmenter of Liver Regeneration (ALR) by Regulating HNF4α Independent of c-Jun.International journal of molecular sciences · 2023Article
- RIPK3 promoter hypermethylation in hepatocytes protects from bile acid-induced inflammation and necroptosis.Cell death & disease · 2023Article
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- Targeted metabolomics reveals aberrant profiles of serum bile acids in patients with schizophrenia.Schizophrenia (Heidelberg, Germany) · 2022Article
- Crosstalk of hepatocyte nuclear factor 4a and glucocorticoid receptor in the regulation of lipid metabolism in mice fed a high-fat-high-sugar diet.Lipids in health and disease · 2022Article
- Discovery of farnesoid X receptor and its role in bile acid metabolism.Molecular and cellular endocrinology · 2022Review
- Effect of microplastics on Yersinia ruckeri infection in rainbow trout (Oncorhynchus mykiss).Environmental science and pollution research international · 2022Article
- Bile acid production is life-stage and sex-dependent and affected by primer pheromones in the sea lamprey.The Journal of experimental biology · 2021Article
28 more citing papers are in PubMed but not listed here.
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3 authors.
Funding
Abstract
Cholesterol 7 alpha-hydroxylase (CYP7A1) of the bile acid biosynthesis pathway is suppressed by bile acids and inflammatory cytokines. Bile acids are known to induce inflammatory cytokines to activate the mitogen-activated protein kinase/c-Jun N-terminal kinase (JNK) signaling pathway that inhibits CYP7A1 gene transcription. c-Jun has been postulated to mediate bile acid inhibition of CYP7A1. However, the c-Jun target involved in the regulation of CYP7A1 is unknown. Human primary hepatocytes and HepG2 cells were used as models to study chenodeoxycholic acid (CDCA) and interleukin-1 beta (IL-1 beta) regulation of human CYP7A1 gene expression via real-time polymerase chain reaction, reporter assays, co-immunoprecipitation and chromatin immunocipitation (ChIP) assays. IL-1 beta and CDCA reduced CYP7A1 but induced c-Jun messenger RNA expression in human primary hepatocytes. IL-1beta inhibited human CYP7A1 reporter activity via the HNF4 alpha binding site. A JNK-specific inhibitor blocked the inhibitory effect of IL-1 beta on HNF4 alpha expression and CYP7A1 reporter activity. c-Jun inhibited HNF4 alpha and PPARgamma coactivator-1 alpha (PGC-1 alpha) coactivation of CYP7A1 reporter activity, whereas a dominant negative c-Jun did not. Co-immunoprecipitation and ChIP assays revealed that IL-1 beta and CDCA reduced HNF4 alpha bound to the CYP7A1 chromatin, and that c-Jun interacted with HNF4 alpha and blocked HNF4 alpha recruitment of PGC-1 alpha to the CYP7A1 chromatin. In conclusion, IL-1 beta and CDCA inhibit HNF4 alpha but induce c-Jun, which in turn blocks HNF 4 alpha recruitment of PGC-1 alpha to the CYP7A1 chromatin and results in inhibition of CYP7A1 gene transcription. The JNK/c-Jun signaling pathway inhibits bile acid synthesis and protects hepatocytes against the toxic effect of inflammatory agents.
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