Two NSAIDs, nimesulide and naproxen, can reduce the synthesis of urokinase and IL-6 while increasing PAI-1, in human OA synovial fibroblasts.
OBJECTIVE
To evaluate the effect of therapeutic and pharmacologic concentrations of two non-steroidal anti-inflammatory drugs (NSAIDs), nimesulide and naproxen, on the synthesis of urokinase (uPA), plasminogen activator inhibitor (PAI-1) and interleukin-6 (IL-6) in human synovial fibroblasts isolated from osteoarthritis (OA) patients.


METHODS
Urokinase, PAI-1, and IL-6 production were measured by specific ELISA.


RESULTS
Nimesulide and naproxen induced a dose-dependent decrease in uPA synthesis. The two drugs, at therapeutic concentrations, exerted a stimulatory effect on the synthesis of PAI-1 whereas the synthesis of IL-6 was significantly reduced by both NSAIDs.


CONCLUSIONS
The results of this study indicate some of the mechanisms by which nimesulide and naproxen could exert their effects on the arthritis process. The suppressive action of the two drugs on the synthesis of uPA, while stimulating PAI-1 production, may have a positive impact on the balance of plasminogen activator/inhibitor, which could help reduce cartilage catabolism.
Pelletier
J P
JP
Osteoarthritis Research Unit, Louis-Charles Simard Research Center, Notre-Dame Hospital, Montreal, Quebec, Canada.
Mineau
F
F
Fernandes
J
J
Kiansa
K
K
Ranger
P
P
Martel-Pelletier
J
J
D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D008297:Male; D009288:Naproxen / Q000494:pharmacology; D010003:Osteoarthritis / Q000378:metabolism*; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology; D013582:Synovial Fluid / Q000166:cytology; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015850:Interleukin-6; D017395:Plasminogen Activator Inhibitor 1; D013449:Sulfonamides; D009288:Naproxen; D014568:Urokinase-Type Plasminogen Activator; C012655:nimesulide