Il-18 induces pro-fibrotic renal tubular cell injury via stat3 activation.

IL-18 INDUCES PRO-FIBROTIC RENAL TUBULAR CELL INJURY VIA STAT3 ACTIVATION. Am J Physiol Renal Physiol. 2013 Jul 31; Authors: Matsui F, Rhee A, Hile KL, Zhang H, Meldrum KK Abstract IL-18 is an important mediator of obstruction-induced renal fibrosis and renal tubular epithelial cell (TEC) injury. IL-18's pro-inflammatory properties have been attributed, in part, to NFκB activation and the stimulation of cytokine gene expression, however, STAT3 has increasingly been shown to mediate renal fibrotic injury. We therefore hypothesized that IL-18 mediates pro-fibrotic TEC injury via STAT3 activation. Male C57BL6 wild-type mice and transgenic mice for human IL-18-binding protein were subjected to unilateral ureteral obstruction or sham operation. The kidneys were harvested 1 or 2 weeks after operation, and analyzed for active STAT3 (p-STAT3) expression (western blot, immunohistochemistry) and suppressor of cytokine signaling 3 (SOCS3) expression. In a separate arm, renal tubular cells (HK-2) were directly stimulated with IL-18 for 2 days with or without the STAT3 inhibitor, S3I-201 (50μM). Cell lysates were then analyzed for p-STAT3 and SOCS3 expression, pro-fibrotic cellular changes (collagen and α-SMA expression), and tubular cell apoptosis. p-STAT3 and SOCS3 expression increased significantly in response to obstruction, however, a significant reduction in p-STAT3 and SOCS3 expression occurred following 1 week, but not 2 weeks, of obstruction in the...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research

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Source: Expert Review of Anti-Infective Therapy - Category: Infectious Diseases Tags: Expert Rev Anti Infect Ther Source Type: research
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Source: Expert Review of Anti-Infective Therapy - Category: Infectious Diseases Tags: Expert Rev Anti Infect Ther Source Type: research
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Source: Expert Review of Anti-Infective Therapy - Category: Infectious Diseases Tags: Expert Rev Anti Infect Ther Source Type: research
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Source: Expert Review of Anti-Infective Therapy - Category: Infectious Diseases Tags: Expert Rev Anti Infect Ther Source Type: research
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