title: Combined inhibition of nitrergic and prostanoid pathways in J774 macrophages.
abstract: OBJECTIVE
  Nitric oxide and prostaglandins are both implicated in the pathogenesis of inflammatory conditions such as rheumatoid arthritis (RA). The hypothesis that simultaneous inhibition of nitric oxide synthase (NOS) and cyclooxygenase (COX) was more effective than inhibition of either enzyme alone was tested.
  
  
  METHODS
  J774 macrophages were pre-incubated with L-NAME and/or indomethacin, prior to activation with LPS (10 micrograms/ml).
  
  
  RESULTS
  LPS significantly increased NO2-; PGE2 and TNF-alpha levels by 24 h. Quantitative real-time PCR demonstrated a dose-dependent reduction in the expression of COX-2 in the presence of increasing doses of L-NAME. NO2- and PGE2 production were inhibited in a dose-dependent manner by either indomethacin or L-NAME. Combined administration of L-NAME and indomethacin produced a significantly greater inhibition of NO2- and PGE2 than either inhibitor alone.
  
  
  CONCLUSIONS
  The data supports the therapeutic potential of combined inhibition of the prostanoid and nitrergic systems as an anti-inflammatory treatment strategy and supports the progression of this work into models of arthritis.
authors: University of Paisley, Paisley.
authors: S M
authors: SM
authors: Day
authors: J S
authors: JS
authors: McLean
authors: J C
authors: JC
authors: Lockhart
authors: W R
authors: WR
authors: Ferrell
mesh_terms: D002478:Cells, Cultured; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000096:biosynthesis; D007213:Indomethacin / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000201:enzymology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D009573:Nitrites / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D016861:Cyclooxygenase Inhibitors; D008070:Lipopolysaccharides; D009573:Nitrites; D014409:Tumor Necrosis Factor-alpha; D019001:Nitric Oxide Synthase; D015232:Dinoprostone; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin