Regulation of cyclooxygenase-2 expression in human mesangial cells -: transcriptional inhibition by IL-13

Activated mesangial cells may play an important part in glomerulonephritis. Cytokines can modulate the release of prostanoids by human mesangial cells (HMC). We have investigated the effects of pro-inflammatory stimuli on COX-2 expression in HMC and its potential modulation by interleukin (IL)-13. HMC released increased amounts of prostaglandin E-2 (PGE(3)) after treatment with several combinations of IL-1 beta, tumor necrosis factor (TNF)-alpha and/or lipopolysaccharide. Increases in PGE(2) correlated with the induction of COS-2 protein expression, The accumulation of PGE(2) elicited by a combination of IL-1 beta/TNF-alpha correlated closely with the temporal pattern of COX-2, protein expression, which reflected the induction of COS-2 mRNA, IL-13 inhibited IL-1 beta/TNF-alpha-elicitcd PGE(2) production, as well as COX-2 protein and mRNA expression in a concentration-dependent fashion. With 50 ng mL(-1) IL-13 these parameters were inhibited by 90, 80 and 84%, respectively In HMC transfected with the 5' regulatory region of the COX-2 gene, IL-13 suppressed cytokine-induced promoter activation. Our results suggest that COX-2 expression is a major target for IL-13-mediated abrogation of prostaglandin release by HMC and support that this process takes place by transcriptional inhibition of the COX-2 gene.