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

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.