NSAIDs increase GM-CSF release by human synoviocytes: comparison with nitric oxide-donating derivatives

摘要: Non-steroidal anti-inflammatory drugs (NSAIDs) are used to treat the condition of rheumatoid arthritis, where levels prostaglandin E2 (PGE2) and granulocyte macrophage-colony stimulating factor (GM-CSF) elevated in synovial fluid. NO-NSAIDs a new class cyclooxygenase (COX)-inhibitors developed by coupling nitric oxide (NO)-donating moiety conventional NSAIDs. We show that, cytokine-treated synoviocytes (from non-rheumatic patients), NO-naproxen NO-flurbiprofen like their parent compounds concentration-dependently reduce PGE2 (an index COX-2 activity), with corresponding rise release GM-CSF. Unlike acetylsalicylic acid (ASA), NO-ASA reduces PGE2, without increasing GM-CSF release, although cell viability is reduced at highest concentration (1 mM). The effects NSAIDs on were attributable mediated cyclic (c) AMP pathway because reversed COX blockade. Second, phosphodiesterase inhibitors 3-isobutyl-1-methylxanthine (IBMX) Ro-201724 (both which elevate cAMP levels) decreased presence PGE2. Finally, neither sodium nitroprusside nor zaprinast cGMP affected or release. Our findings demonstrate that regulated via inhibition appears be pathway. exception, it does not increase millimolar concentrations reduced.