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Whereas toxicity is initiated by hepatocyte necrosis, course of disease is regulated by mechanisms of innate immunity having the potential to serve in complex manner pathogenic or pro-regenerative functions. Interleukin (IL)-36\u03b3 has been identified as novel IL-1-like cytokine produced by and targeting epithelial (-like) tissues. Herein, we investigated IL-36\u03b3 in acute liver disease focusing on murine APAP-induced hepatotoxicity. Enhanced expression of hepatic IL-36\u03b3 and its prime downstream chemokine target CCL20 was detected upon liver injury. CCL20 expression coincided with the later regeneration phase of intoxication. Primary murine hepatocytes and human Huh7 hepatocellular carcinoma cells indeed displayed enhanced IL-36\u03b3 expression when exposed to inflammatory cytokines. Administration of IL-36 receptor antagonist (IL-36Ra) decreased hepatic CCL20 in APAP-treated mice. Unexpectedly, IL-36Ra likewise increased late phase hepatic injury as detected by augmented serum alanine aminotransferase activity and histological necrosis which suggests disturbed tissue recovery upon IL-36 blockage. Finally, we demonstrate induction of IL-36\u03b3 in inflamed livers of endotoxemic mice. Observations presented introduce IL-36\u03b3 as novel parameter in acute liver injury which may contribute to the decision between unleashed tissue damage and initiation of liver regeneration during late APAP toxicity.<\/jats:p>","DOI":"10.1038\/srep08521","type":"journal-article","created":{"date-parts":[[2015,2,17]],"date-time":"2015-02-17T10:32:15Z","timestamp":1424169135000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Application of IL-36 receptor antagonist weakens CCL20 expression and impairs recovery in the late phase of murine acetaminophen-induced liver injury"],"prefix":"10.1038","volume":"5","author":[{"given":"Patrick","family":"Scheiermann","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malte","family":"Bachmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorena","family":"H\u00e4rdle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Pleli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albrecht","family":"Piiper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernhard","family":"Zwissler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josef","family":"Pfeilschifter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heiko","family":"M\u00fchl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,2,17]]},"reference":[{"key":"BFsrep08521_CR1","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1016\/S0140-6736(10)60274-7","volume":"376","author":"W Bernau","year":"2010","unstructured":"Bernau, W., Auzinger, G., Dhawan, A. & Wendon, J. 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