{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T20:19:17Z","timestamp":1789935557267,"version":"4.0.1"},"reference-count":35,"publisher":"American Physiological Society","issue":"3","funder":[{"name":"NIH","award":["R01 DK59615"],"award-info":[{"award-number":["R01 DK59615"]}]},{"name":"NIH","award":["R01 AA21171"],"award-info":[{"award-number":["R01 AA21171"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2017,9,1]]},"abstract":"<jats:p>\n                    Interleukin-22 (IL-22) is a Th17 cell hepatoprotective cytokine that is undergoing clinical trials to treat patients with alcoholic hepatitis (AH). Lipopolysaccharide (LPS) activation of macrophage is implicated in hepatocyte cell death and pathogenesis of AH. The role of IL-22 production from macrophage, its regulation by LPS, and effects on alcohol-induced hepatocyte cell death are unexplored and were examined in this study. Low levels of IL-22 mRNA\/protein were detected in macrophage but were significantly upregulated by 6.5-fold in response to the tissue reparative cytokine IL-10. Conversely, LPS significantly decreased IL-22 mRNA levels in a temporal and concentration-dependent manner with a maximum reduction of 5-fold. LPS downregulation of IL-22 mRNA levels was rescued in the presence of a pharmacological inhibitor of c-Jun NH\n                    <jats:sub>2<\/jats:sub>\n                    -terminal kinase (JNK) and by JNK knockdown. Next, we explored whether macrophage-derived IL-22 regulated ethanol-induced hepatocyte death. Conditioned media from IL-10-stimulated macrophages attenuated ethanol-induced hepatocyte caspase-3\/7 activity, and apoptosis as assessed by fluorometric assay and TdT-mediated dUTP nick-end labeling (TUNEL) staining, respectively. This effect was diminished in conditioned media from macrophages with IL-22 knockdown. Cytokine analysis in sera samples of patients with AH revealed that IL-22 levels were significantly elevated compared with healthy controls and heavy-drinking controls, implying a state of IL-22 resistance in human AH. Macrophage-derived IL-22 protects hepatocytes from ethanol-induced cell death. IL-22 downregulation is a new regulatory target of LPS in the pathogenesis of AH.\n                  <\/jats:p>","DOI":"10.1152\/ajpcell.00005.2017","type":"journal-article","created":{"date-parts":[[2017,6,21]],"date-time":"2017-06-21T21:10:21Z","timestamp":1498079421000},"page":"C305-C313","source":"Crossref","is-referenced-by-count":32,"title":["Lipopolysaccharide downregulates macrophage-derived IL-22 to modulate alcohol-induced hepatocyte cell death"],"prefix":"10.1152","volume":"313","author":[{"given":"Yaming","family":"Liu","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology Mayo Clinic, Rochester, Minnesota;"},{"name":"The First Hospital of Jilin University, Changchun, Jilin Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vikas K.","family":"Verma","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Mayo Clinic, Rochester, Minnesota;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harmeet","family":"Malhi","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Mayo Clinic, Rochester, Minnesota;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greg J.","family":"Gores","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Mayo Clinic, Rochester, Minnesota;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick S.","family":"Kamath","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Mayo Clinic, Rochester, Minnesota;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arun","family":"Sanyal","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Virginia Commonwealth University, Richmond, Virginia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naga","family":"Chalasani","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Indiana University, Indianapolis, Indiana;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Gao","sequence":"additional","affiliation":[{"name":"Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7620-573X","authenticated-orcid":false,"given":"Vijay H.","family":"Shah","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Mayo Clinic, Rochester, Minnesota;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3791\/50765"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.11.7551"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2015.12.019"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00683"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-032414-112123"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1746.2011.07003.x"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2011.09.002"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2004.053850"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-013-0608-1"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.4.2219"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/nature18644"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2012.11.001"},{"key":"B13","first-page":"251","volume":"37","author":"Ju C","year":"2015","journal-title":"Alcohol Res"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/495156"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23837"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.12032"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1038\/nri3088"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2016.05.041"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2006.118059"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1610"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-4906(02)02302-5"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.4065\/76.10.1021"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21060"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23009"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2012.06.004"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00151.2013"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2015.94"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1093\/femspd\/ftw111"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2015.11.020"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0034355"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26607"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.03.009"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2007.02.001"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2010.08.002"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(00)00047-7"}],"container-title":["American Journal of Physiology-Cell Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.physiology.org\/doi\/pdf\/10.1152\/ajpcell.00005.2017","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T12:09:22Z","timestamp":1718626162000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.physiology.org\/doi\/10.1152\/ajpcell.00005.2017"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,9,1]]},"references-count":35,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2017,9,1]]}},"alternative-id":["10.1152\/ajpcell.00005.2017"],"URL":"https:\/\/doi.org\/10.1152\/ajpcell.00005.2017","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.727743931.793536753","asserted-by":"object"}]},"ISSN":["0363-6143","1522-1563"],"issn-type":[{"value":"0363-6143","type":"print"},{"value":"1522-1563","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,9,1]]}}}