Induction of nitric oxide synthase in human mesangial cells

A G Nicolson, N E Haites, N G McKay, H M Wilson, A M MacLeod, N Benjamin

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69 Citations (Scopus)


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.
Original languageEnglish
Pages (from-to)1269-74
Number of pages6
JournalBiochemical and Biophysical Research Communications
Issue number3
Publication statusPublished - 30 Jun 1993


  • Amino Acid Oxidoreductases
  • Arginine
  • Cell Survival
  • Cells, Cultured
  • Cycloheximide
  • Cytokines
  • Dexamethasone
  • Enzyme Induction
  • Glomerular Mesangium
  • Humans
  • Interferon-gamma
  • Interleukin-1
  • Kinetics
  • Lipopolysaccharides
  • NG-Nitroarginine Methyl Ester
  • Nitric Oxide Synthase
  • Tumor Necrosis Factor-alpha
  • omega-N-Methylarginine


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