Endogenous nitric oxide and prostaglandin E2 do not regulate the synthesis of each other in interleukin-1 beta-stimulated rat articular cartilage.
Increased levels of nitric oxide (NO) and prostaglandins (PG) are present in the synovial fluid from patients with rheumatoid arthritis and osteoarthritis. Interleukin-1 beta (IL-1) has been shown to induce the synthesis of both of these mediators. The present work was designed to study the interactions of NO and PGE2 synthesis induced by IL-1 in rat articular cartilage. Incubation of intact cartilage with IL-1 resulted in different dose response curves for NO and PGE2 synthesis. Two inhibitors of nitric oxide synthase N-monomethyl-L-arginine (L-NMMA) and L-N-iminoethylornithine, (L-NIO), abolished the IL-1-induced nitrite production but failed to have any influence on the PGE2 synthesis. Exogenous NO, produced by two chemically different NO-releasing compounds (SIN-1 and GEA 3175) had no effect on PGE2 synthesis in articular cartilage. Dexamethasone and ketoprofen inhibited IL-1 induced PGE2 production, while nitrite synthesis remained unaltered. Acetylsalicylic acid (ASA) reduced PGE2 synthesis and had a slight inhibitory action also on NO production. In conclusion, our results show, that IL-1 induces the synthesis of both PGE2 and NO in articular cartilage but these two inflammatory mediators are not mediating the synthesis of one another.
Järvinen
T A
TA
Medical School, University of Tampere, Finland.
Moilanen
T
T
Järvinen
T L
TL
Moilanen
E
E
D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D002358:Cartilage, Articular / Q000187:drug effects* / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis* / Q000494:pharmacology*; D003576:Electron Transport Complex IV / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology*; D007660:Ketoprofen / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009924:Organ Culture Techniques; D009952:Ornithine / Q000031:analogs & derivatives / Q000494:pharmacology; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014230:Triazoles / Q000494:pharmacology; D019323:omega-N-Methylarginine / Q000494:pharmacology
C093084:GEA 3175; D007375:Interleukin-1; D011448:Prostaglandin Antagonists; D014230:Triazoles; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; C065027:N(G)-iminoethylornithine; C002385:linsidomine; D003907:Dexamethasone; D007660:Ketoprofen; D008981:Molsidomine; D009952:Ornithine; D019001:Nitric Oxide Synthase; D003576:Electron Transport Complex IV; D015232:Dinoprostone; D001241:Aspirin