Interleukin 1 beta and tumour necrosis factor alpha induce a macrophage-type 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 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.
Ciba-Geigy Ltd. Research Department, Pharmaceuticals Division, Basel, Switzerland.
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J
Pfeilschifter
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Rob
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A
Mülsch
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J
Fandrey
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K
Vosbeck
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R
Busse
D000594:Amino Acid Oxidoreductases / Q000096:biosynthesis*; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism; D004790:Enzyme Induction; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D007375:Interleukin-1 / Q000494:pharmacology*; D008264:Macrophages / Q000201:enzymology*; D019001:Nitric Oxide Synthase; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D000804:Angiotensin II; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D006152:Cyclic GMP