Nimphy, Jonas and Ibrahim, Sara and Dayoub, Rania and Kubitza, Marion and Melter, Michael and Weiss, Thomas S. (2023) Interleukin-1ss Attenuates Expression of Augmenter of Liver Regeneration (ALR) by Regulating HNF4a Independent of c-Jun. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 24 (9): 8107. ISSN , 1422-0067
Full text not available from this repository. (Request a copy)Abstract
Inflammasomes and innate immune cells have been shown to contribute to liver injury, thereby activating Kupffer cells, which release several cytokines, including IL-6, IL-1ss, and TNFa. Augmenter of liver regeneration (ALR) is a hepatotropic co-mitogen that was found to have anti-oxidative and anti-apoptotic properties and to attenuate experimental non-alcoholic fatty liver disease (NAFLD) and cholestasis. Additionally, hepatic ALR expression is diminished in patients with NAFLD or cholestasis, but less is known about the mechanisms of its regulation under these conditions. Therefore, we aimed to investigate the role of IL-1ss in ALR expression and to elucidate the molecular mechanism of this regulation in vitro. We found that ALR promoter activity and mRNA and protein expression were reduced upon treatment with IL-1ss. Early growth response protein-1 (Egr-1), an ALR inducer, was induced by IL-1ss but could not activate ALR expression, which may be attributed to reduced Egr-1 binding to the ALR promoter. The expression and nuclear localization of hepatocyte nuclear factor 4 a (HNF4a), another ALR-inducing transcription factor, was reduced by IL-1ss. Interestingly, c-Jun, a potential regulator of ALR and HNF4a, showed increased nuclear phosphorylation levels upon IL-1ss treatment but did not change the expression of ALR or HNF4a. In conclusion, this study offers evidence regarding the regulation of anti-apoptotic and anti-oxidative ALR by IL-1ss through reduced Egr-1 promoter binding and diminished HNF4a expression independent of c-Jun activation. Low ALR tissue levels in NAFLD and cholestatic liver injury may be caused by IL-1ss and contribute to disease progression.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HEPATIC STIMULATOR SUBSTANCE; DOWN-REGULATION; BILE-ACIDS; OXIDATIVE STRESS; GENE-EXPRESSION; KUPFFER CELLS; INFLAMMATION; PROMOTER; PATHWAY; SP1; augmenter of liver regeneration; IL-1ss; inflammation; NAFLD; cholestasis; cytokine |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Kinder- und Jugendmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 08 Mar 2024 09:02 |
| Last Modified: | 08 Mar 2024 09:02 |
| URI: | https://pred.uni-regensburg.de/id/eprint/59046 |
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