title: Innate immune mechanisms in ischemia/reperfusion.
abstract: Ischemia/reperfusion (I/R) injury remains a major problem in solid organ transplantation, as it adversely impacts both short and long term outcomes. It has been well established that the innate immune system plays a significant role in the pathogenesis of I/R injury. In contrast, the proximal molecular signaling events that initiate activation of the innate immune system are less clear. Recent findings have demonstrated that Toll-like receptors (TLR) play a role in I/R injury. Specifically, TLR4 is central to early activation of the innate immune response in the setting of I/R. Furthermore, recent evidence has shown that endogenous molecules, such as high mobility group box-1 (HMGB1) and others that are released from ischemic, damaged, or dying cells and tissues in the setting I/R, can serve as triggers for activation of the innate immune system and exacerbate tissue injury. This evolving body of literature, which has provided insight into the early molecular events that activate the innate system after I/R, is reviewed here.
authors.affiliation: Department of Surgery, University of Pittsburgh School of Medicine, 200 Lothrop Street, Presbyterian Hospital F1200, Pittsburgh, PA 15213, USA. billiartr@upmc.edu
authors.forename: David J
authors.initials: DJ
authors.lastname: Kaczorowski
authors.forename: Allan
authors.initials: A
authors.lastname: Tsung
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Billiar
mesh_terms: D024002:HMGB Proteins / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D007249:Inflammation / Q000209:etiology / Q000276:immunology*; D007668:Kidney / Q000276:immunology / Q000473:pathology*; D008099:Liver / Q000276:immunology / Q000473:pathology*; D008168:Lung / Q000276:immunology / Q000473:pathology*; D009206:Myocardium / Q000276:immunology / Q000473:pathology*; D015427:Reperfusion Injury / Q000150:complications / Q000276:immunology / Q000503:physiopathology*; D051197:Toll-Like Receptor 4 / Q000276:immunology*
chemical_list: D024002:HMGB Proteins; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4