VanderBrink, Brian A.Asanuma, HiroshiHile, KarenZhang, HonjiRink, Richard C.Meldrum, Kirstan K.2018-04-062018-04-062011-10VanderBrink, B. A., Asanuma, H., Hile, K., Zhang, H., Rink, R. C., & Meldrum, K. K. (2011). IL-18 STIMULATES A POSITIVE FEEDBACK LOOP DURING RENAL OBSTRUCTION VIA THE IL-18 RECEPTOR. The Journal of Urology, 186(4), 1502–1508. http://doi.org/10.1016/j.juro.2011.05.046https://hdl.handle.net/1805/15772PURPOSE: Interleukin-18 is a proinflammatory cytokine that is an important mediator of obstruction induced renal tubulointerstitial fibrosis independent of tumor necrosis factor-α and β1 activity. We hypothesized that interleukin-18 stimulates a positive feedback loop during obstruction via interleukin-18 receptor to increase interleukin-18 gene expression and protein production. MATERIALS AND METHODS: Male C57BL6 interleukin-18 receptor knockout (The Jackson Laboratory, Bar Harbor, Maine) and control wild-type mice underwent unilateral ureteral obstruction or sham operation and were sacrificed 1 week after surgery. Renal cortical tissue samples were harvested and analyzed for interleukin-18 protein by enzyme-linked immunosorbent assay, and for interleukin-18 and interleukin-18 receptor gene expression by quantitative polymerase chain reaction. The specific cellular localization of interleukin-18 and interleukin-18 receptor expression during obstruction was assessed using dual labeling immunofluorescence staining. RESULTS: Renal interleukin-18 receptor expression increased significantly in wild-type mice in response to obstruction but remained at sham operation levels in interleukin-18 receptor knockout mice. Similarly while interleukin-18 protein and gene expression were significantly increased in wild-type mice in response to obstruction, interleukin-18 levels and gene expression were significantly decreased during obstruction in knockout mice. Obstruction induced interleukin-18 and interleukin-18 receptor production were localized predominantly to tubular epithelial cells and to a lesser extent to the renal interstitium. CONCLUSIONS: Results reveal that interleukin-18 stimulates a positive feedback loop via interleukin-18 receptor during renal obstruction to stimulate interleukin-18 production and gene expression. The predominant cellular source of interleukin-18 production during renal obstruction appears to be tubular epithelial cells rather than infiltrating macrophages.en-USPublisher PolicyInterleukin-18KidneyObstructionLocalizationArticle