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 Wu Qing, Christopher Y. Lu

Research output: Contribution to journalArticle

36 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1544-1555
Number of pages12
JournalJournal of the American Society of Nephrology
Volume20
Issue number7
DOIs
StatePublished - Jul 2009

ASJC Scopus subject areas

  • Nephrology

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    Wang, Y., John, R., Chen, J., Richardson, J. A., Shelton, J. M., Bennett, M., Zhou, X. J., Nagami, G. T., Zhang, Y., Qing, Q. W., & Lu, C. Y. (2009). IRF-1 promotes inflammation early after ischemic acute kidney injury. Journal of the American Society of Nephrology, 20(7), 1544-1555. https://doi.org/10.1681/ASN.2008080843