title: Flurbiprofen enantiomers inhibit inducible nitric oxide synthase expression in RAW 264.7 macrophages.
abstract: OBJECTIVE
  Using RAW 264.7 macrophages, the present study investigates the influence of optically pure enantiomers of the nonsteroidal anti-inflammatory drug flurbiprofen on lipopolysaccharide (LPS)-induced inducible nitric oxide synthase (iNOS) expression.
  
  
  METHODS
  iNOS and cyclooxygenase-2 (COX-2) mRNA levels were measured by quantitative real-time reverse-transcription polymerase chain reaction (RT-PCR). Concentrations of nitrite (index of cellular NO production) and prostaglandin E2 (index of COX-2 activity) in cell culture supernatants were determined by Griess assay and enzyme immunoassay, respectively.
  
  
  RESULTS
  R(-)- and S(+)-flurbiprofen decreased LPS-induced iNOS mRNA and nitrite levels in an equipotent and concentration-dependent manner. Suppression of iNOS mRNA expression by R(-)- and S(+)-flurbiprofen was gene-specific in that both substances failed to inhibit LPS-induced COX-2 mRNA expression. By contrast, flurbiprofen enantiomers suppressed LPS-induced prostaglandin E2 formation enantioselectively with S(+)-flurbiprofen being considerably more potent than its R(-)-antipode.
  
  
  CONCLUSIONS
  Our results show that R(-)- and S(+)-flurbiprofen, albeit differing in their potency as inhibitors of COX-2 activity, equipotently suppress iNOS expression. Because sustained high NO levels are associated with pain and tissue injury under various pathological conditions, a suppression of the inducible NO pathway may contribute to the pharmacological action of both R(-)- and S(+)-flurbiprofen.
authors.affiliation: Department of Experimental and Clinical Pharmacology and Toxicology, Friedrich Alexander University Erlangen-Nürnberg, Germany. hinz@pharmakologie.uni-erlangen.de
authors.forename: B
authors.initials: B
authors.lastname: Hinz
authors.forename: K
authors.initials: K
authors.lastname: Brune
authors.forename: T
authors.initials: T
authors.lastname: Rau
authors.forename: A
authors.initials: A
authors.lastname: Pahl
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D005480:Flurbiprofen / Q000737:chemistry / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology; D051379:Mice; D008968:Molecular Conformation; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II
chemical_list: D016861:Cyclooxygenase Inhibitors; D005480:Flurbiprofen; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse