Treatment of rat renal mesangial cells with IL-1 beta or TNF alpha induced nitric oxide synthase, increasing cGMP formation and attenuating the contractile response to angiotensin II.
Does treatment with IL-1 beta or TNF alpha induce nitric oxide synthase and increase cGMP formation in rat renal mesangial cells?
IL-1 beta and TNF alpha induce a macrophage-type nitric oxide synthase in rat renal mesangial cells, leading to increased cGMP formation and attenuated contractile responses to angiotensin II.
Treatment of mesangial cells with interleukin 1 beta (IL-1 beta) or tumour necrosis factor alpha (TNF alpha) has been shown to increase cGMP formation, most probably due to induction of nitric oxide synthase. Here we report that maximum stimulation of cGMP formation over a 24-h period required the presence of IL-1 beta or TNF alpha during the first 18 h of induction. N4-monomethyl-L-arginine (L-NMMA) was a potent inhibitor of cytokine-induced cGMP formation while N4-nitro-L-arginine (L-NNA) was less active. Formation of nitric oxide was detected in the cytosol of cytokine-treated mesangial cells by activation of purified soluble guanylate cyclase and was stimulated by tetrahydrobiopterin, but not by calcium calmodulin. Treatment of cells with IL-1 beta or TNF alpha markedly attenuated the contractile response to a subsequent challenge with angiotensin II. Furthermore, conditioned medium from IL-1 beta-treated cells increased cGMP in untreated control cells.
Pfeilschifter et al. (Wed,) conducted a other in Rat renal mesangial cells. Interleukin 1 beta (IL-1 beta) or tumour necrosis factor alpha (TNF alpha) vs. Untreated control cells was evaluated on cGMP formation. Treatment of rat renal mesangial cells with IL-1 beta or TNF alpha induced nitric oxide synthase, increasing cGMP formation and attenuating the contractile response to angiotensin II.