IRF-1 promotes inflammation early after ischemic acute kidney injury.
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.
Wang
Yanxia
Y
Department of Internal Medicine-Nephrology, University of Texas Southwestern Medical School, 5323 Harry Hines Boulevard, Dallas, TX 75390-8856, USA.
John
Reji
R
Chen
Jianlin
J
Richardson
James A
JA
Shelton
John M
JM
Bennett
Michael
M
Zhou
Xin J
XJ
Nagami
Glenn T
GT
Zhang
Ying
Y
Wu
Qing Qing
QQ
Lu
Christopher Y
CY
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
D050856:Interferon Regulatory Factor-1; D012333:RNA, Messenger; D017382:Reactive Oxygen Species