Regulation of prostaglandin production in an immortalized human myometrial cell line by cytokines and non-steroidal anti-inflammatory drugs

Abstract

Objective: To test the effect of selective and non-selective inhibitors of prostaglandin H synthase-2 (PGHS-II) on basal and cytokine-stimulated prostaglandin (PG) production by the immortalized human myometrial cell line, UTLRp16. Study Design: UTLRp16 cells were treated with interleukin (IL)-1β (0.1, 1, 10ng/ml) and tumor necrosis factor (TNF)-α (1, 3, 10ng/ml) in the presence or absence of indomethacin, etodolac, 5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulphonyl) phenyl-2 (5H)-furanone (DFU) or nimesulide for 16h (1.6–1000nM). PG production was then measured by radioimmunoassay. Results: IL-1β and TNF-α both stimulated production of PGE2 and 6-keto-PGF1α in a concentration-dependent manner. DFU showed the most PGHS-II selectivity with IL-β-stimulated PG production, with a IC50basal/IC50stimulated ratio of 177.8, followed by nimesulide (122.5), etodolac (23.5) and indomethacin (2.7). DFU was not as selective in TNF-α stimulated cells (ratio 99.5). Conclusion: PGHS-II-selective inhibitors may be effective in the prevention of cytokine-driven myometrial PG production associated with preterm labor.