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  • Title: Regulation of prostaglandin production in an immortalized human myometrial cell line by cytokines and non-steroidal anti-inflammatory drugs.
    Author: Sato TA, Keelan JA, Mitchell MD.
    Journal: Eur J Obstet Gynecol Reprod Biol; 2002 Jan 10; 100(2):158-62. PubMed ID: 11750956.
    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)-1beta (0.1, 1, 10ng/ml) and tumor necrosis factor (TNF)-alpha (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-1beta and TNF-alpha both stimulated production of PGE(2) and 6-keto-PGF(1alpha) in a concentration-dependent manner. DFU showed the most PGHS-II selectivity with IL-beta-stimulated PG production, with a IC(50)(basal)/IC(50)(stimulated) ratio of 177.8, followed by nimesulide (122.5), etodolac (23.5) and indomethacin (2.7). DFU was not as selective in TNF-alpha 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.
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