{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T12:58:45Z","timestamp":1782997125769,"version":"3.54.5"},"reference-count":41,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Gastrointestinal and Liver Physiology"],"published-print":{"date-parts":[[2012,9,1]]},"abstract":"<jats:p>Interferon regulatory factor (IRF)-1 is a nuclear transcription factor that induces inflammatory cytokine mediators and contributes to hepatic ischemia-reperfusion (I\/R) injury. No strategies to mitigate IRF1-mediated liver damage exist. IRF2 is a structurally similar endogenous protein that competes with IRF1 for DNA binding sites in IRF-responsive target genes and acts as a competitive inhibitor. However, the role of IRF2 in hepatic injury during hypoxic or inflammatory conditions is unknown. We hypothesize that IRF2 overexpression may mitigate IRF1-mediated I\/R damage. Endogenous IRF2 is basally expressed in normal livers and is mildly increased by ischemia alone. Overexpression of IRF2 protects against hepatic warm I\/R injury. Furthermore, we demonstrate that IRF2 overexpression limits production of IRF1-dependent proinflammatory genes, such as IL-12, IFN\u03b2, and inducible nitric oxide synthase, even in the presence of IRF1 induction. Additionally, isograft liver transplantation with IRF2 heterozygote knockout (IRF2<jats:sup>+\/\u2212<\/jats:sup>) donor grafts that have reduced endogenous IRF2 levels results in worse injury following cold I\/R during murine orthotopic liver transplantation. These findings indicate that endogenous intrahepatic IRF2 protein is protective, because the IRF2-deficient liver donor grafts exhibited increased liver damage compared with the wild-type donor grafts. In summary, IRF2 overexpression protects against I\/R injury by decreasing IRF1-dependent injury and may represent a novel therapeutic strategy.<\/jats:p>","DOI":"10.1152\/ajpgi.00050.2012","type":"journal-article","created":{"date-parts":[[2012,6,30]],"date-time":"2012-06-30T00:14:06Z","timestamp":1341015246000},"page":"G666-G673","source":"Crossref","is-referenced-by-count":36,"title":["Interferon regulatory factor-2 is protective against hepatic ischemia-reperfusion injury"],"prefix":"10.1152","volume":"303","author":[{"given":"John R.","family":"Klune","sequence":"first","affiliation":[{"name":"Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajeev","family":"Dhupar","sequence":"additional","affiliation":[{"name":"Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh, Pittsburgh, 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