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The present study focuses on the mechanisms by which interleukin 1 \u03b2 (IL-1\u03b2), as a critical mediator of sepsis-induced cholestasis, controls the expression of BSEP in hepatocytes. Notably, the treatment of hepatocytes with IL-1\u03b2 leads to the upregulation of a broad chemokine pattern. Thereby, the IL-1\u03b2 -induced expression of in particular the CXCR2 ligands CXCL1 and 2 is further enhanced by bile acids, whereas the FXR-mediated upregulation of BSEP induced by bile acids is inhibited by IL-1\u03b2. In this context, it is interesting to note that inhibitor studies indicate that IL-1\u03b2 mediates its inhibitory effects on bile acid-induced expression of BSEP indirectly via CXCR2 ligands. Consistently, inhibition of CXCR2 with the inhibitor SB225002 significantly attenuated of the inhibitory effect of IL-1\u03b2 on BSEP expression. These data suggest that part of the cholestasis-inducing effect of IL-1\u03b2 is mediated via a CXCR2-dependent feedback mechanism.<\/jats:p>","DOI":"10.1371\/journal.pone.0315243","type":"journal-article","created":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T18:30:58Z","timestamp":1734373858000},"page":"e0315243","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Interleukin 1 \u03b2 suppresses bile acid-induced BSEP expression via a CXCR2-dependent feedback mechanism"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-4264-0582","authenticated-orcid":true,"given":"Carolin","family":"Angendohr","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leah","family":"Missing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0103-1856","authenticated-orcid":true,"given":"Christian","family":"Ehlting","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie D.","family":"Wolf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl 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