Production of prostanoids via increased cyclo-oxygenase-2 expression in human amnion cells in response to low molecular weight hyaluronic acid fragment.
Increased concentrations of hyaluronic acid (HA) have been found in serum and at uterine cervix at term. In its native form, HA exists as a high molecular weight (MW) polymer, but during parturition a lower MW HA fragment accumulates. The aim of this study was to investigate the regulatory mechanisms responsible for increased amnion prostanoid production and cyclo-oxygenase (COX) expression in response to HA. Human term amnion cells in culture were exposed to native HA polymer (MW 2.2x106) and its fragment (MW 3.5x104). We have determined levels of prostanoids, prostaglandins E2 and F2alpha, in conditioned media using specific immunoassays. Expression of COX-1 and COX-2 was examined with Western blot. Results were analyzed for statistical significance with Mann-Whitney U-test. Human amnion cells treated with HA fragment (100 nmol/l) produced significantly more PGE2 (2.3+/-0.21 (mean+/-S.D.) pg/106 cells/24 h) than controls (0.34+/-0.03) or high MW HA-treated cells (1.2+/-0.21). Protein levels of COX-2, but not COX-1, were substantially increased in amnion cells treated with HA fragment. HA fragment-mediated prostanoid production is markedly diminished by pretreatment with indomethacin. Our results indicate that HA fragment, rather than physiologic native HA polymer, induces amnion cell-derived prostanoid production via increased COX-2 expression. COX-2-mediated prostanoid production is likely a key physiologic event in HA fragment-mediated cervical ripening and the labor onset.
Kobayashi
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Department of Obstetrics and Gynecology, Hamamatsu University School of Medicine, Handacho 3600, Hamamatsu, Shizuoka 431-3192, Japan.
Sun
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GW
Terao
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D000650:Amnion / Q000187:drug effects* / Q000378:metabolism; D015153:Blotting, Western; D002478:Cells, Cultured; D020070:Cervical Ripening / Q000502:physiology; D051546:Cyclooxygenase 2; D015237:Dinoprost / Q000096:biosynthesis*; D015232:Dinoprostone / Q000096:biosynthesis*; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D007527:Isoenzymes / Q000096:biosynthesis*; D008565:Membrane Proteins; D008970:Molecular Weight; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D013997:Time Factors
D007527:Isoenzymes; D008565:Membrane Proteins; D006820:Hyaluronic Acid; D015237:Dinoprost; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D007213:Indomethacin