Efficacy and specificity of non-steroidal anti-inflammatory drugs for the inhibition of cytokine-stimulated prostaglandin E(2) secretion by amnion-derived WISH cells.
Prostaglandin H synthase-2 (PGHS-II) specific inhibitors have been proposed as a potential treatment in the prevention of preterm birth. We examined the efficacy of PGHS inhibitors on basal and cytokine-stimulated prostaglandin (PG) production by the amnion-like WISH cell line. WISH cells were treated with interleukin (IL)-1 beta and tumour necrosis factor (TNF)-alpha in the presence or absence of indomethacin, etodolac, 5,5-dimethy-3-(3-fluorophenyl)-4-(4-methlysulphonyl) phenyl-2 (5H)-furanone (DFU) or nimesulide (1.6-1000 nM) for 16 h. PG production was then measured using radioimmunoassay. Nimesulide and DFU were the most selective non-steroidal anti-inflammatory drugs (NSAIDs) of IL-beta-stimulated PG production in these studies with an a IC(50)(basal)/IC(50)(stimulated) ratio of, respectively, 142.2 and 113.8, followed by etodolac (25.3) and indomethacin (2.2). Similar results were obtained when cells were stimulated with TNF-alpha. The results of this study suggest that PGHS-II-selective NSAIDs may be effective in the prevention of cytokine-driven amnion PG production associated with preterm labour.
Sato
T A
TA
Faculty of Medical and Health Sciences, Division of Pharmacology and Clinical Pharmacology, Liggins Institute, University of Auckland, Auckland, New Zealand. t.sato@auckland.ac.nz
Keelan
J A
JA
Blumenstein
M
M
Mitchell
M D
MD
D000650:Amnion / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002478:Cells, Cultured; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D007375:Interleukin-1 / Q000494:pharmacology; D011458:Prostaglandins E / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D016207:Cytokines; D007375:Interleukin-1; D011458:Prostaglandins E; D014409:Tumor Necrosis Factor-alpha