2008 JASN IMPACT FACTOR 7.505	HOME   AUTHOR INFO   EDITORIAL BOARD   SUBSCRIBE   FEEDBACK   ALERTS   HELP
advanced	CURRENT ISSUE	ARCHIVES	JASN Express	ONLINE SUBMISSION

This Article Full Text Full Text (PDF) All Versions of this Article: ASN.2008080843v1 20/7/1544    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Wang, Y. Articles by Lu, C. Y. PubMed PubMed Citation Articles by Wang, Y. Articles by Lu, C. Y.

IRF-1 Promotes Inflammation Early after Ischemic Acute Kidney Injury

Yanxia Wang^*, Reji John^*, Jianlin Chen^*, James A. Richardson^,, John M. Shelton^,, Michael Bennett, Xin J. Zhou, Glenn T. Nagami, Ying Zhang^*, Qing Qing Wu^* and Christopher Y. Lu^*,||

^* Nephrology and Cardiology, Department of Internal Medicine, Department of Pathology, and ^|| Graduate Program in Immunology, University of Texas Southwestern Medical Center, Dallas, Texas; and the Nephrology Section, VA Greater Los Angeles and University of California, Los Angeles, Los Angeles, California

Correspondence: Dr. Christopher Y. Lu, Department of Internal Medicine (Nephrology), University of Texas Southwestern Medical School, 5323 Harry Hines Boulevard, Dallas, TX 75390-8856. Phone: 214-648-3959; Fax: 214-648-2071; E-mail: christopher.lu{at}utsouthwestern.edu

Received for publication August 11, 2008. Accepted for publication March 5, 2009.

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.

Copyright © 2009 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673