title: Role of Toll-like receptor-4 in renal graft ischemia-reperfusion injury.
abstract: Toll-like receptor-4 (TLR-4) has been increasingly recognized as playing a critical role in the pathogenesis of ischemia-reperfusion injury (IRI) of renal grafts. This review provides a detailed overview of the new understanding of the involvement of TLR-4 in ischemia-reperfusion injury of renal grafts and its clinical significance in renal transplantation. TLR-4 not only responds to exogenous microbial motifs but can also recognize molecules which are released by stressed and necrotic cells, as well as degraded products of endogenous macromolecules. Upregulation of TLR-4 is found in tubular epithelial cells, vascular endothelial cells, and infiltrating leukocytes during renal ischemia-reperfusion injury, which is induced by massive release of endogenous damage-associated molecular pattern molecules such as high-mobility group box chromosomal protein 1. Activation of TLR-4 promotes the release of proinflammatory mediators, facilitates leukocyte migration and infiltration, activates the innate and adaptive immune system, and potentiates renal fibrosis. TLR-4 inhibition serves as the target of pharmacological agents, which could attenuate ischemia-reperfusion injury and associated delayed graft function and allograft rejection. There is evidence in the literature showing that targeting TLR-4 could improve long-term transplantation outcomes. Given the pivotal role of TLR-4 in ischemia-reperfusion injury and associated delayed graft function and allograft rejection, inhibition of TLR-4 using pharmacological agents could be beneficial for long-term graft survival.
authors: Anaesthetics, Pain Medicine, and Intensive Care, Dept. of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea and Westminster Hospital, London, UK. d.ma@imperial.ac.uk.
authors: Hailin
authors: H
authors: Zhao
authors: Jessica Santiváñez
authors: JS
authors: Perez
authors: Kaizhi
authors: K
authors: Lu
authors: Andrew J T
authors: AJ
authors: George
authors: Daqing
authors: D
authors: Ma
mesh_terms: D000818:Animals; D058578:Biglycan / Q000502:physiology; D006084:Graft Rejection; D024243:HMGB1 Protein / Q000502:physiology; D006360:Heat-Shock Proteins / Q000502:physiology; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology; D016030:Kidney Transplantation / Q000009:adverse effects*; D007683:Kidney Tubular Necrosis, Acute / Q000209:etiology; D053594:Myeloid Differentiation Factor 88 / Q000502:physiology; D011110:Polymorphism, Genetic; D015427:Reperfusion Injury / Q000503:physiopathology*; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000502:physiology*
chemical_list: D058578:Biglycan; D024243:HMGB1 Protein; D006360:Heat-Shock Proteins; D053594:Myeloid Differentiation Factor 88; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4
keywords: Toll-like receptor 4; delayed graft function; ischemia-reperfusion injury; renal graft failure; renal transplantation