{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T04:47:20Z","timestamp":1771649240551,"version":"3.50.1"},"reference-count":41,"publisher":"American Physiological Society","issue":"6","funder":[{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health (NIH)","doi-asserted-by":"publisher","award":["HHSN276201200017C"],"award-info":[{"award-number":["HHSN276201200017C"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Gastrointestinal and Liver Physiology"],"published-print":{"date-parts":[[2018,12,1]]},"abstract":"<jats:p> Interleukin-23 (IL-23) is a proinflammatory cytokine initially studied in autoimmune disease that has been more recently linked to innate immunity. We observed that the expression of IL-23 is upregulated during hypoxia in a hepatocyte and nonparenchymal cell (NPC) coculture system, as well as during ischemia-reperfusion (I\/R) injury in the liver. Interferon regulatory factor-1 (IRF-1) is a transcription factor that induces expression of multiple inflammatory cytokines and has been shown to play a critical role in liver I\/R injury. We observed that IL-23 signaling induces not only the IL-17\/chemokine (C-X-C motif) ligand 2 (CXCL2) pathway but also the IFN-\u03b3\/IRF-1 pathway. Quantification of cytokine genes revealed increased liver expression of IL-17a, CXCL2, and IRF-1 messenger RNA during liver transplantation. Recombinant IL-23 treated hepatocytes, and NPC coculture led to IL-17, CXCL2, IFN-\u03b3, and IRF-1 expression. With anti-IL-17 and anti-Ly6G antibody neutralization, neutrophil recruitment and IFN-\u03b3 production were decreased during warm I\/R injury. Overexpression of IL-23 in vivo through use of an adenovirus vector also led to expression of IL-17, CXCL2, IFN-\u03b3, and IRF-1. The increased expression of IL-23 also led to increased apoptosis in the liver. By neutralization of IL-23 through use of an anti-IL-23p19 antibody, we were able to attenuate liver damage in a wild-type but not a natural killer T (NKT) cell-deficient mouse. This suggests that IL-23 signaling shares a common pathway with NKT cells. In conclusion, IL-23 is induced early by I\/R in the liver. Its signaling leads to activation of the IL-17\/CXCL2 and IFN-\u03b3\/IRF-1 pathways, resulting in increased apoptosis and necrosis. <\/jats:p><jats:p> NEW &amp; NOTEWORTHY IL-23 is expressed early during cold ischemia-reperfusion (I\/R), and this expression is associated with expression of IL-17 and chemokine (C-X-C motif) ligand 2. Neutralization of IL-23 during cold I\/R can significantly reduce liver damage as well as decrease cytokine production and neutrophil infiltration in the liver. IL-23 appears to activate IFN-\u03b3 production in natural killer T cells within the liver which, in turn, activates interferon regulatory factor-1, a known inflammatory transcription factor during I\/R injury. <\/jats:p>","DOI":"10.1152\/ajpgi.00231.2018","type":"journal-article","created":{"date-parts":[[2018,10,11]],"date-time":"2018-10-11T15:21:46Z","timestamp":1539271306000},"page":"G991-G1002","source":"Crossref","is-referenced-by-count":23,"title":["IL-23 mediates murine liver transplantation ischemia-reperfusion injury via IFN-\u03b3\/IRF-1 pathway"],"prefix":"10.1152","volume":"315","author":[{"given":"John R.","family":"Klune","sequence":"first","affiliation":[{"name":"Thomas E. 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