{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T12:17:13Z","timestamp":1753877833890,"version":"3.41.2"},"reference-count":37,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T00:00:00Z","timestamp":1730246400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["21K09471"],"award-info":[{"award-number":["21K09471"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP22gk0210028"],"award-info":[{"award-number":["JP22gk0210028"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Rep Immunol"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Problem<\/jats:title><jats:p>What is the effect of SR\u201016234 (SR), a selective estrogen receptor (ER) modulator, on human endometriotic stromal cells (ESCs)?<\/jats:p><\/jats:sec><jats:sec><jats:title>Method of Study<\/jats:title><jats:p>Endometriotic tissues were obtained from 21 patients undergoing laparoscopic surgery for ovarian endometriomas (OEs). Normal eutopic endometrium during the luteal phase was obtained from 18 patients without endometriosis. ESCs isolated from OEs and normal eutopic endometrial stromal cells (NESCs) were cultured with SR and subsequently exposed to tumor necrosis factor (TNF)\u2010\u03b1. After 48 h of incubation, the effect of SR on cell proliferation was evaluated by the WST\u20108 assay. The gene expressions of inflammatory and pain\u2010related factors, including <jats:italic>interleukin<\/jats:italic> (<jats:italic>IL<\/jats:italic>)<jats:italic>\u20106<\/jats:italic>, <jats:italic>IL\u20108<\/jats:italic>, <jats:italic>cyclooxygenase<\/jats:italic> (<jats:italic>COX<\/jats:italic>)<jats:italic>\u20102<\/jats:italic>, <jats:italic>transient receptor potential vanilloid<\/jats:italic> (<jats:italic>TRPV<\/jats:italic>)<jats:italic>1<\/jats:italic>, <jats:italic>ESR1<\/jats:italic>, and <jats:italic>ESR2<\/jats:italic>, were evaluated by real\u2010time RT\u2010PCR. The phosphorylation of Inhibitor \u03baB\u03b1 (I\u03baB\u03b1), extracellular signal\u2010regulated kinase (ERK)1\/2, and Protein Kinase B (AKT) were evaluated by western blot analysis. ILs, prostaglandin (PG) E2, and intranuclear p65 syntheses were assessed by ELISA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>SR treatment repressed TNF\u2010\u03b1\u2010induced proliferation by 20% in ESCs but not\u3000NESCs. SR also reduced <jats:italic>IL\u20106<\/jats:italic>, <jats:italic>IL\u20108<\/jats:italic>, <jats:italic>COX\u20102<\/jats:italic>, <jats:italic>TRPV1<\/jats:italic>, <jats:italic>ESR1<\/jats:italic>, and <jats:italic>ESR2<\/jats:italic> mRNA expressions and ILs protein, and PGE2 synthesis in ESCs, whereas in NESCs, only <jats:italic>TRPV1<\/jats:italic> mRNA expression was decreased. SR suppressed TNF\u2010\u03b1\u2010induced phosphorylated I\u03baB\u03b1 levels by approximately 50%, and intranuclear p65 protein was reduced by 30% compared to addition of only TNF\u2010\u03b1 in ESCs. However, SR did not affect the phosphorylation of AKT and ERK1\/2.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>SR appears to be a potential therapeutic agent for endometriosis by suppressing inflammatory and pain\u2010related factor expressions by inhibiting the nuclear factor\u2010kappa B pathway.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aji.70010","type":"journal-article","created":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T17:53:07Z","timestamp":1730310787000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["SR\u201016234, a Unique Selective Estrogen Receptor Modulator, Suppressed Proliferation and Pain\u2010Related Factor Expression by Inhibition of the Nuclear Factor\u2010kappa B Pathway in Endometriotic Stromal Cells"],"prefix":"10.1111","volume":"92","author":[{"given":"Emiko","family":"Yamane","sequence":"first","affiliation":[{"name":"Division of Obstetrics and 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