Regulation of nitric oxide and prostaglandin E2 production by CSAIDS (SB203580) in murine macrophages and bovine chondrocytes stimulated with LPS

Inflamm Res. 1999 Jun;48(6):337-43. doi: 10.1007/s000110050469.

Abstract

Objective and design: To compare two anti-inflammatory drugs: CSAIDS (SB203580) and hydrocortisone on iNOS and COX-2 expression.

Material or subjects: Murine macrophages and bovine chondrocytes stimulated with LPS and human OA-affected cartilage were used in this study.

Treatment: The macrophages and chondrocytes were preincubated (30 min) with 0.1-1.0 microM CSAIDS or 10 microM of hydrocortisone before stimulating them with 1-100 microg/ml LPS.

Methods: The end products of iNOS and COX-2: nitric oxide (NO) and PGE2 were estimated by Greiss method and RIA, respectively.

Results: CSAIDS (1 microM) inhibited the production of NO and PGE2 (p< or =0.01) in bovine chondrocytes, but not in murine macrophages (RAW 264.7) (p< or =0.1). In fact, CSAIDS (in murine macrophages) marginally augmented nitrite accumulation (approximately 20%) at 14-24 h of LPS stimulation. Western blot analysis of COX-2 in bovine chondrocytes show decrease in COX-2 expression by hydrocortisone but not CSAIDS, although hydrocortisone and CSAIDS inhibit PGE2 accumulation. Hydrocortisone inhibited both PGE2 and NO production significantly (p< or =0.01) in murine macrophages. Furthermore, hydrocortisone significantly inhibited (p< or =0.01) PGE2 but marginally (p< or =0.05) NO in bovine chondrocytes.

Conclusion: These experiments demonstrate differential action of CSAIDS and hydrocortisone on NO and PGE2 production in bovine chondrocytes and RAW 264.7 cells.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Cattle
  • Cell Line
  • Chondrocytes / drug effects*
  • Chondrocytes / metabolism
  • Cyclooxygenase 2
  • Dinoprostone / biosynthesis*
  • Humans
  • Hydrocortisone / pharmacology*
  • Imidazoles / pharmacology*
  • Isoenzymes / biosynthesis
  • Isoenzymes / drug effects
  • Lipopolysaccharides / immunology
  • Macrophages / drug effects*
  • Macrophages / metabolism
  • Membrane Proteins
  • Mice
  • Nitric Oxide / metabolism*
  • Prostaglandin-Endoperoxide Synthases / biosynthesis
  • Prostaglandin-Endoperoxide Synthases / drug effects
  • Pyridines / pharmacology*

Substances

  • Anti-Inflammatory Agents
  • Imidazoles
  • Isoenzymes
  • Lipopolysaccharides
  • Membrane Proteins
  • Pyridines
  • Nitric Oxide
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • Dinoprostone
  • SB 203580
  • Hydrocortisone