Induction of nitric oxide synthase in human mesangial cells.
Synthesis of nitric oxide (NO) has been implicated in the development of glomerulonephritis in animal models of the disease. Rat mesangial cells can be stimulated to express an inducible form of NO synthase (NOS) in vitro. Little is known however, about the pathway of induction in human mesangial cells. Here, we report that human mesangial cells require multiple cytokines, unlike rat mesangial cells which require only single stimulants, to produce NO. Our experiments suggest that both interleukin-1 beta (IL-1 beta) and interferon gamma (IFN-gamma) must be present together to elicit a response whilst tumour necrosis factor alpha (TNF-alpha) augments this. The production of nitrite, a stable end product of NO metabolism, was inhibited by NG-monomethyl-L-arginine (L-NMMA), L-nitro-arginine-methyl-ester (L-NAME), cycloheximide and the glucocorticoid dexamethasone.
Nicolson
A G
AG
Department of Medicine and Therapeutics, University of Aberdeen Medical School, Foresterhill, Scotland.
Haites
N E
NE
McKay
N G
NG
Wilson
H M
HM
MacLeod
A M
AM
Benjamin
N
N
D000594:Amino Acid Oxidoreductases / Q000096:biosynthesis*; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002470:Cell Survival; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology; D004790:Enzyme Induction; D005920:Glomerular Mesangium / Q000187:drug effects / Q000201:enzymology*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019323:omega-N-Methylarginine
D016207:Cytokines; D007375:Interleukin-1; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D019323:omega-N-Methylarginine; D003907:Dexamethasone; D007371:Interferon-gamma; D001120:Arginine; D003513:Cycloheximide; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D019331:NG-Nitroarginine Methyl Ester