It has long been known that prostaglandins (PGEs) play a key role in the regulation of the parturition by stimulating uterine contractility. Recently , nitric oxide (NO), a short-lived radical generated from L-arginine by nitric oxide synthase (NOS), and responsible of several biologic actions, has been identified among the factors involved in uterine activity modulation. NO, as well as prostaglandins, is produced not only by miometrium, but also by placental tissue and fetal membranes, where NOS is expressed. It has been established that interleukin-1 beta (IL-1 beta) is able to increase the expression of inducible isoform of both cyclooxygenase (COX) and NOS (iNOS) in inflammation mediating cells, and in rat uterus. The aim of this study was to better clarify the relationship between NO and PGE2 pathways in human amnion-like WISH cells, which represent a useful model to study gestational prostanoid metabolism. Our results indicate that: 1) sodium nitroprusside (SNP), a NO donor, increases spontaneous PGE2 release in a dose-dependent manner, while it inhibits IL-1 beta induced output of the prostanoid; 2) L-arginine, the substrate of NOS, does not influence PGE2 output from both resting and IL-1 beta treated cells; 3) IL-1 beta treatment does not induce the expression of iNOS; 4) indomethacin, a cyclooxygenase inhitor that drastically reduces basal PGE2 level and counteracts IL-1 beta induced prostaglandin output, allows the expression of the iNOS; 5) betametrhasone, which partially inhibits IL-1 beta induced PGE2 output as well as COX-2 expression, enhances iNOS mRNA level; 6) exogenous PGE2 prevents the effects induced by indomethacin treatment. These results clearly demonstrate the presence of a negative feedback control by PGE2 on iNOS expression in amnion-like WISH cells.

Cross-talk between nitridergic and prostaglandinergic pathways in amnion-like WISH cells

PAVAN, Barbara;VESCE, Fortunato;BIONDI, Carla
2002

Abstract

It has long been known that prostaglandins (PGEs) play a key role in the regulation of the parturition by stimulating uterine contractility. Recently , nitric oxide (NO), a short-lived radical generated from L-arginine by nitric oxide synthase (NOS), and responsible of several biologic actions, has been identified among the factors involved in uterine activity modulation. NO, as well as prostaglandins, is produced not only by miometrium, but also by placental tissue and fetal membranes, where NOS is expressed. It has been established that interleukin-1 beta (IL-1 beta) is able to increase the expression of inducible isoform of both cyclooxygenase (COX) and NOS (iNOS) in inflammation mediating cells, and in rat uterus. The aim of this study was to better clarify the relationship between NO and PGE2 pathways in human amnion-like WISH cells, which represent a useful model to study gestational prostanoid metabolism. Our results indicate that: 1) sodium nitroprusside (SNP), a NO donor, increases spontaneous PGE2 release in a dose-dependent manner, while it inhibits IL-1 beta induced output of the prostanoid; 2) L-arginine, the substrate of NOS, does not influence PGE2 output from both resting and IL-1 beta treated cells; 3) IL-1 beta treatment does not induce the expression of iNOS; 4) indomethacin, a cyclooxygenase inhitor that drastically reduces basal PGE2 level and counteracts IL-1 beta induced prostaglandin output, allows the expression of the iNOS; 5) betametrhasone, which partially inhibits IL-1 beta induced PGE2 output as well as COX-2 expression, enhances iNOS mRNA level; 6) exogenous PGE2 prevents the effects induced by indomethacin treatment. These results clearly demonstrate the presence of a negative feedback control by PGE2 on iNOS expression in amnion-like WISH cells.
prostaglandins, nitric oxide, interleukin 1-β, COX-2; iNOS, WISH cells
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/1738239
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