title: Review article: the role of tumor necrosis factor in renal ischemia-reperfusion injury.
abstract: Renal ischemia-reperfusion injury induces a cascade of events leading to cellular damage and organ dysfunction. Tumor necrosis factor-alpha (TNF), a potent proinflammatory cytokine, is released from the kidney in response to, and has been implicated in the pathogenesis of, renal ischemia-reperfusion injury. TNF induces glomerular fibrin deposition, cellular infiltration and vasoconstriction, leading to a reduction in glomerular filtration rate (GFR). The signaling cascade through which renal ischemia-reperfusion induces TNF production is beginning to be elucidated. Oxidants released following reperfusion activate p38 mitogen activated protein kinase (p38 MAP kinase) and the TNF transcription factor, NFkappaB, leading to subsequent TNF synthesis. In a positive feedback, proinflammatory fashion, binding of TNF to specific TNF membrane receptors can reactivate NFkappaB. This provides a mechanism by which TNF can upregulate its own expression as well as facilitate the expression of other genes pivotal to the inflammatory response. TNF receptor binding can also induce renal cell apoptosis, the major form of cell death associated with renal ischemia-reperfusion injury. Anti-TNF strategies targeting p38 MAP kinase, NFkappaB, and TNF itself are being investigated as methods of attenuating renal ischemic injury. The control of TNF production and activity represents a realistic goal for clinical medicine.
authors.affiliation: Department of Urology, Indiana University Medical Center, Indianapolis, USA.
authors.forename: K K
authors.initials: KK
authors.lastname: Donnahoo
authors.forename: B D
authors.initials: BD
authors.lastname: Shames
authors.forename: A H
authors.initials: AH
authors.lastname: Harken
authors.forename: D R
authors.initials: DR
authors.lastname: Meldrum
mesh_terms: D017209:Apoptosis; D006801:Humans; D007668:Kidney / Q000098:blood supply* / Q000473:pathology; D015427:Reperfusion Injury / Q000209:etiology* / Q000628:therapy; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
chemical_list: D014409:Tumor Necrosis Factor-alpha