{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T01:38:35Z","timestamp":1792201115255,"version":"4.4.0"},"reference-count":48,"publisher":"The Endocrine Society","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2006,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Spontaneous labor in women and in other mammals is likely mediated by a concerted series of biochemical events that negatively impact the ability of the progesterone receptor (PR) to regulate target genes that maintain myometrial quiescence. In the present study, we tested the hypothesis that progesterone\/PR inhibits uterine contractility by blocking nuclear factor \u03baB (NF-\u03baB) activation and induction of cyclooxygenase-2 (COX-2), a contractile gene that is up-regulated in labor. To uncover mechanisms for regulation of uterine COX-2, immortalized human fundal myometrial cells were treated with IL-1\u03b2 \u00b1 progesterone. IL-1\u03b2 alone caused a marked up-regulation of COX-2 mRNA, whereas treatment with progesterone suppressed this induction. This was also observed in human breast cancer (T47D) cells. In both cell lines, this inhibitory effect of progesterone was blocked by RU486. Using chromatin immunoprecipitation, we observed that IL-1\u03b2 stimulated recruitment of NF-\u03baB p65 to both proximal and distal NF-\u03baB elements of the COX-2 promoter; these effects were diminished by coincubation with progesterone. The ability of progesterone to inhibit COX-2 expression in myometrial cells was associated with rapid induction of mRNA and protein levels of inhibitor of \u03baB\u03b1, a protein that blocks NF-\u03baB transactivation. Furthermore, small interfering RNA-mediated ablation of both PR-A and PR-B isoforms in T47D cells greatly enhanced NF-\u03baB activation and COX-2 expression. These effects were observed in the absence of exogenous progesterone, suggesting a ligand-independent action of PR. Based on these findings, we propose that PR may inhibit NF-\u03baB activation of COX-2 gene expression and uterine contractility via ligand-dependent and ligand-independent mechanisms.<\/jats:p>","DOI":"10.1210\/me.2006-0112","type":"journal-article","created":{"date-parts":[[2006,6,14]],"date-time":"2006-06-14T04:04:24Z","timestamp":1150257864000},"page":"2724-2733","source":"Crossref","is-referenced-by-count":254,"title":["Progesterone Receptor Plays a Major Antiinflammatory Role in Human Myometrial Cells by Antagonism of Nuclear Factor-\u03baB Activation of Cyclooxygenase 2 Expression"],"prefix":"10.1210","volume":"20","author":[{"given":"Daniel B.","family":"Hardy","sequence":"first","affiliation":[{"name":"Departments of Biochemistry (D.B.H., D.R.C., C.R.M.), Dallas, Texas 75390-9038"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bethany A.","family":"Janowski","sequence":"additional","affiliation":[{"name":"Pharmacology (B.A.J., D.R.C.), North Texas March of Dimes Birth Defects Center, The University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390-9038"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R.","family":"Corey","sequence":"additional","affiliation":[{"name":"Departments of Biochemistry (D.B.H., D.R.C., C.R.M.), Dallas, Texas 75390-9038"},{"name":"Pharmacology (B.A.J., D.R.C.), North Texas March of Dimes Birth Defects Center, The University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390-9038"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carole R.","family":"Mendelson","sequence":"additional","affiliation":[{"name":"Departments of Biochemistry (D.B.H., D.R.C., C.R.M.), Dallas, Texas 75390-9038"},{"name":"Obstetrics and Gynecology (C.R.M.), Dallas, Texas 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