Differential regulation of interleukin-1 beta-induced cyclooxygenase-2 gene expression by nimesulide in human synovial fibroblasts

Clin Exp Rheumatol. 2001;19(1 Suppl 22):S3-5.

Abstract

Osteoarthritic (OA) human synovial fibroblasts (HSF) in culture were treated with the preferential COX-2 inhibitors nimesulide or NS-398, the non-specific COX-1/COX-2 inhibitor naproxen, or dexamethasone, in the presence or absence of IL-1 beta or LPS. Nimesulide or NS-398 inhibited IL-1 beta-induced PGE2 production at all concentrations tested, and in addition they suppressed IL-1 beta-induced COX-2 mRNA expression and protein synthesis. These suppressive effects were most evident at therapeutic levels of the drugs. Mechanistic studies revealed that the drug-induced inhibition of COX-2 expression and synthesis was not promoter-based, but may be associated with the blockade of IL-1 beta-dependent calcium flux and increased cellular calcium levels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arthritis, Rheumatoid / drug therapy
  • Arthritis, Rheumatoid / enzymology
  • Arthritis, Rheumatoid / surgery
  • Cells, Cultured
  • Cyclooxygenase 2
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors / pharmacology*
  • Dexamethasone / pharmacology
  • Dinoprostone / biosynthesis
  • Dinoprostone / genetics
  • Dose-Response Relationship, Drug
  • Down-Regulation / drug effects
  • Fibroblasts / drug effects
  • Fibroblasts / enzymology*
  • Fibroblasts / pathology
  • Gene Expression Regulation, Enzymologic / drug effects*
  • Humans
  • Interleukin-1 / pharmacology
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / genetics*
  • Lipopolysaccharides / pharmacology
  • Membrane Proteins
  • Naproxen / pharmacology
  • Nitrobenzenes / pharmacology
  • Osteoarthritis / drug therapy
  • Osteoarthritis / enzymology
  • Osteoarthritis / surgery
  • Prostaglandin-Endoperoxide Synthases / genetics*
  • RNA, Messenger / biosynthesis
  • Sulfonamides / pharmacology*
  • Synovial Membrane / drug effects
  • Synovial Membrane / enzymology*
  • Synovial Membrane / pathology

Substances

  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors
  • Interleukin-1
  • Isoenzymes
  • Lipopolysaccharides
  • Membrane Proteins
  • Nitrobenzenes
  • RNA, Messenger
  • Sulfonamides
  • N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide
  • Naproxen
  • Dexamethasone
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • Dinoprostone
  • nimesulide