Transforming growth factor beta 2 inhibits interleukin 1 beta- and tumour necrosis factor alpha-induction of nitric oxide synthase in rat renal mesangial cells.

Treatment of mesangial cells with interleukin 1 beta (IL-1 beta) or tumour necrosis factor alpha (TNF alpha) has been shown to induce nitric oxide (NO) synthase with subsequent autocrine stimulation of soluble guanylate cyclase (Pfeilschifter and Schwarzenbach, 1990, FEBS Lett. 273, 185-187). Here we report that transforming growth factor beta 2 (TGF beta 2) dose-dependently inhibits IL-1 beta- and TNF alpha-stimulated cGMP formation in mesangial cells. Half-maximal inhibition is observed at concentrations of 0.4 and 0.06 ng/ml of TGF beta 2, respectively. Maximum inhibition of cGMP formation over a 24 h period requires the presence of TGF beta 2 during the first 4 h of induction. In addition, the inhibitory effect of TGF beta 2 on cytokine-induced cGMP formation is not affected by the potent cyclo-oxygenase inhibitor indomethacin, thus excluding prostaglandins as mediators.