IRF-1 Promotes Inflammation Early after Ischemic Acute Kidney Injury

AUTOR(ES)

Wang, Yanxia

FONTE

American Society of Nephrology

RESUMO

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.

Documentos Relacionados

• Activation of IFN-beta element by IRF-1 requires a posttranslational event in addition to IRF-1 synthesis.
• Early exposure to germs modifies kidney damage and inflammation after experimental ischemia-reperfusion injury
• Dynamic Changes in Perioperative Cellular Inflammation and Acute Kidney Injury after Coronary Artery Bypass Grafting
• Urinary Biomarkers in the Early Detection of Acute Kidney Injury after Cardiac Surgery
• TLR7 mediates increased vulnerability to ischemic acute kidney injury in diabetes