title: IRF-1 promotes inflammation early after ischemic acute kidney injury.
abstract: Acute renal ischemia elicits an inflammatory response that may exacerbate acute kidney injury, but the regulation of the initial signals that recruit leukocytes is not well understood. Here, we found that IFN regulatory factor 1 (IRF-1) was a critical, early proinflammatory signal released during ischemic injury in vitro and in vivo. Within 15 min of reperfusion, proximal tubular cells of the S3 segment produced IRF-1, which is a transcription factor that activates proinflammatory genes. Transgenic knockout of IRF-1 ameliorated the impairment of renal function, morphologic injury, and inflammation after acute ischemia. Bone marrow chimera experiments determined that maximal ischemic injury required IRF-1 expression by both leukocytes and radioresistant renal cells, the latter identified as S3 proximal tubule cells in the outer medulla by in situ hybridization and immunohistochemistry. In vitro, reactive oxygen species, generated during ischemia/reperfusion injury, stimulated expression of IRF-1 in an S3 proximal tubular cell line. Taken together, these data suggest that IRF-1 gene activation by reactive oxygen species is an early signal that promotes inflammation after ischemic renal injury.
authors.affiliation: Department of Internal Medicine-Nephrology, University of Texas Southwestern Medical School, 5323 Harry Hines Boulevard, Dallas, TX 75390-8856, USA.
authors.forename: Yanxia
authors.initials: Y
authors.lastname: Wang
authors.forename: Reji
authors.initials: R
authors.lastname: John
authors.forename: Jianlin
authors.initials: J
authors.lastname: Chen
authors.forename: James A
authors.initials: JA
authors.lastname: Richardson
authors.forename: John M
authors.initials: JM
authors.lastname: Shelton
authors.forename: Michael
authors.initials: M
authors.lastname: Bennett
authors.forename: Xin J
authors.initials: XJ
authors.lastname: Zhou
authors.forename: Glenn T
authors.initials: GT
authors.lastname: Nagami
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Qing Qing
authors.initials: QQ
authors.lastname: Wu
authors.forename: Christopher Y
authors.initials: CY
authors.lastname: Lu
mesh_terms: D058186:Acute Kidney Injury / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D050856:Interferon Regulatory Factor-1 / Q000235:genetics / Q000378:metabolism*; D007511:Ischemia / Q000378:metabolism* / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000502:physiology
chemical_list: D050856:Interferon Regulatory Factor-1; D012333:RNA, Messenger; D017382:Reactive Oxygen Species