title: Naproxen sodium decreases prostaglandins secretion from cultured human endometrial stromal cells modulating metabolizing enzymes mRNA expression.
abstract: Dysmenorrhea, defined as painful cramps occurring immediately before or during the menstrual period, is a common symptom of different gynecological diseases. An acute uterine inflammatory response driven by prostaglandins (PGs) is responsible for painful symptoms. Progesterone withdrawal is responsible for activation of cyclooxygenase (COX-2) enzyme and decrease of hydroxyprostaglandin dehydrogenase (HPDG) with consequent increased secretion of PGs secretion, inducing uterine contractility and pain. The most widely used drugs for the treatment of pelvic pain associated with menstrual cycle are non steroidal anti-inflammatory drugs (NSAIDs). The uterine site of action of these drugs is still not defined and the present study evaluated the effect of naproxen sodium in cultured human endometrial stromal cells (HESC) collected from healthy women. PGE2 release was measured by ELISA; COX-2 and HPDG mRNA expression were assessed by qRT-PCR. Naproxen sodium did not affect HESC vitality. Naproxen sodium significantly decreased PGE2 secretion (p < 0.01) and COX-2 mRNA expression (p < 0.01). TNF-α induced PGE2 release was reduced in presence of naproxen sodium (p < 0.05), in association with decreased COX-2 and increased HPDG mRNAs expression. Naproxen sodium decreases endometrial PGE2 release induced by inflammatory stimulus acting on endometrial COX-2 and HPDG expression, suggesting endometrial synthesis of prostaglandins as a possible target for reduction of uterine inflammatory mechanism in dysmenorrhea.
authors.affiliation: a Division of Obstetrics and Gynecology , Department of Molecular and Developmental Medicine, University of Siena , Siena , Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Carrarelli
authors.affiliation: a Division of Obstetrics and Gynecology , Department of Molecular and Developmental Medicine, University of Siena , Siena , Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Funghi
authors.affiliation: a Division of Obstetrics and Gynecology , Department of Molecular and Developmental Medicine, University of Siena , Siena , Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Bruni
authors.affiliation: a Division of Obstetrics and Gynecology , Department of Molecular and Developmental Medicine, University of Siena , Siena , Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Luisi
authors.affiliation: a Division of Obstetrics and Gynecology , Department of Molecular and Developmental Medicine, University of Siena , Siena , Italy.
authors.forename: Felice
authors.initials: F
authors.lastname: Arcuri
authors.affiliation: a Division of Obstetrics and Gynecology , Department of Molecular and Developmental Medicine, University of Siena , Siena , Italy.
authors.forename: Felice
authors.initials: F
authors.lastname: Petraglia
mesh_terms: D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism*; D004717:Endometrium / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D005260:Female; D006801:Humans; D009288:Naproxen / Q000494:pharmacology*; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D014409:Tumor Necrosis Factor-alpha; D009288:Naproxen; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D015232:Dinoprostone
keywords: Cyclooxygenase-2; dysmenorrhea; hydroxyprostaglandin dehydrogenase; naproxen sodium; prostaglandins