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. H MC 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 inductio n of COS-2 protein expression, The accumulation of PGE(2) elicited by a com bination of IL-1 beta/TNF-alpha correlated closely with the temporal patter n 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 a s COX-2 protein and mRNA expression in a concentration-dependent fashion. W ith 50 ng mL(-1) IL-13 these parameters were inhibited by 90, 80 and 84%, r espectively In HMC transfected with the 5' regulatory region of the COX-2 g ene, IL-13 suppressed cytokine-induced promoter activation. Our results sug gest 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 b y transcriptional inhibition of the COX-2 gene.