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

J.A. Di Battista, H. Fahmi, Y. He, M. Zhang, J. Martel-Pelletier, J.-P. Pelletier

Université de Montreal, and Unité de Recherche en Arthrose, Centre Hospitalier de l'Université de Montreal, Hôpital Notre-Dame, Montréal, Canada.

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-1b or LPS. Nimesulide or NS-398 inhibited IL-1b-induced PGE2 production at all concentrations tested, and in addition they suppressed IL-1b-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-1b-dependent calcium flux and increased cellular calcium levels. 

Key words
COX-2 expression, synovial fibroblasts, nimesulide. 

Supported in part by Helsinn Healthcare S.A. (Lugano-Pazzallo, Switzerland), the Medical Research Council of Canada and the Arthritis Society of Canada.
Please address correspondence to: Jean-Pierre Pelletier, MD, Unité de Recherche en Arthrose, Centre Hospitalier de l'Université de Montreal, Hôpital Notre-Dame, 1560 rue Sherbrooke est, Montréal, Québec, Canada H2L 4M1. 
E-mail: jppelletier@arthrolab.qc.ca

Clin Exp Rheumatol 2001; 19 (Suppl. 22): S3-S5.
© Copyright Clinical and Experimental Rheumatology 2001.