{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:07:19Z","timestamp":1760148439233,"version":"build-2065373602"},"reference-count":64,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,4,30]],"date-time":"2023-04-30T00:00:00Z","timestamp":1682812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the medical school, University of Regensburg Hospital, Regensburg, Germany","award":["DAAD, ID 57169181"],"award-info":[{"award-number":["DAAD, ID 57169181"]}]},{"DOI":"10.13039\/501100001655","name":"German Academic Exchange Service","doi-asserted-by":"publisher","award":["DAAD, ID 57169181"],"award-info":[{"award-number":["DAAD, ID 57169181"]}],"id":[{"id":"10.13039\/501100001655","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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-1\u00df, and TNF\u03b1. 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-1\u00df 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-1\u00df. Early growth response protein-1 (Egr-1), an ALR inducer, was induced by IL-1\u00df 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 \u03b1 (HNF4\u03b1), another ALR-inducing transcription factor, was reduced by IL-1\u00df. Interestingly, c-Jun, a potential regulator of ALR and HNF4\u03b1, showed increased nuclear phosphorylation levels upon IL-1\u00df treatment but did not change the expression of ALR or HNF4\u03b1. In conclusion, this study offers evidence regarding the regulation of anti-apoptotic and anti-oxidative ALR by IL-1\u00df through reduced Egr-1 promoter binding and diminished HNF4\u03b1 expression independent of c-Jun activation. Low ALR tissue levels in NAFLD and cholestatic liver injury may be caused by IL-1\u00df and contribute to disease progression.<\/jats:p>","DOI":"10.3390\/ijms24098107","type":"journal-article","created":{"date-parts":[[2023,5,1]],"date-time":"2023-05-01T13:54:46Z","timestamp":1682949286000},"page":"8107","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Interleukin-1\u00df Attenuates Expression of Augmenter of Liver Regeneration (ALR) by Regulating HNF4\u03b1 Independent of c-Jun"],"prefix":"10.3390","volume":"24","author":[{"given":"Jonas","family":"Nimphy","sequence":"first","affiliation":[{"name":"Children\u2019s University Hospital (KUNO), University Hospital Regensburg, 93053 Regensburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2312-2701","authenticated-orcid":false,"given":"Sara","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Children\u2019s University Hospital (KUNO), University Hospital Regensburg, 93053 Regensburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5848-5571","authenticated-orcid":false,"given":"Rania","family":"Dayoub","sequence":"additional","affiliation":[{"name":"Children\u2019s University Hospital (KUNO), University Hospital Regensburg, 93053 Regensburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marion","family":"Kubitza","sequence":"additional","affiliation":[{"name":"Children\u2019s University Hospital (KUNO), University Hospital Regensburg, 93053 Regensburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Melter","sequence":"additional","affiliation":[{"name":"Children\u2019s University Hospital (KUNO), University Hospital Regensburg, 93053 Regensburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0336-0581","authenticated-orcid":false,"given":"Thomas S.","family":"Weiss","sequence":"additional","affiliation":[{"name":"Children\u2019s University Hospital (KUNO), University Hospital Regensburg, 93053 Regensburg, Germany"},{"name":"Center for Liver Cell Research, University Hospital Regensburg, 93053 Regensburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"R1147","DOI":"10.1016\/j.cub.2017.09.019","article-title":"The liver","volume":"27","author":"Trefts","year":"2017","journal-title":"Curr. 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