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Selective Cyclooxygenase-2 Inhibition Upregulates Renal Cortical αv Integrin Expression

Background: Cyclooxygenase-2 (COX-2), the inducible isoform of the cyclooxygenases, is upregulated in various inflammatory renal diseases and responsible for prostaglandin formation. As prostaglandins are known to influence cell adhesion processes, we investigated the effect of COX-2 inhibition on the expression of αv integrins, which are also enhanced in renal diseases and control the adherence between the endothelium and the extracellular matrix (ECM) in the glomerulus. Methods: Healthy female Wistar rats and animals with previously induced passive Heymann nephritis (PHN) received either 5 mg/kg body weight/day celecoxib or a placebo. After 28 days, renal cortical mRNA expression of COX-2 and αv integrin subunits was determined. Results: Rats with PHN showed a significant 1.7-fold increase in renal cortical mRNA expression of αv integrin subunits. Treatment with celecoxib increased cortical αv integrin mRNA expression 2.2-fold (p < 0.05) in healthy animals and 4.0-fold (p < 0.05) in rats with PHN, but lowered COX-2 mRNA expression in rats with PHN to 0.8-fold (p < 0.05). An inverse correlation between the expression of COX-2 and αv integrins in rats with PHN was demonstrated. Conclusions: It is suggested that COX-2-derived prostaglandins suppress the expression of αv integrins. This implies a previously unknown role for COX-2 in chronic inflammation in the kidney.