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

Objective and Design: To compare two anti-inflammatory drugs: CSAIDSTM (SB 203580) 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 μM CSAIDSTM or 10 μM of hydrocortisone before stimulating them with 1-100 μg/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: CSAIDSTM (1 μM) inhibited the production of NO and PGE2 (p ≤ 0.01) in bovine chondrocytes, but not in murine macrophages (RAW 264.7) (p ≤ 0.1). In fact, CSAIDSTM (in murine macrophages) marginally augmented nitrite accumulation (∼ 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 CSAIDSTM, although hydrocortisone and CSAIDSTM inhibit PGE2 accumulation. Hydrocortisone inhibited both PGE2 and NO production significantly (p ≤ 0.01) in murine macrophages. Furthermore, hydrocortisone significantly inhibited (p ≤ 0.01) PGE2 but marginally (p ≤ 0.05) NO in bovine chondrocytes.¶Conclusion: These experiments demonstrate differential action of CSAIDSTM and hydrocortisone on NO and PGE2 production in bovine chondrocytes and RAW 264.7 cells.