{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T01:42:35Z","timestamp":1790818955365,"version":"4.1.0"},"reference-count":63,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2006,7,17]],"date-time":"2006-07-17T00:00:00Z","timestamp":1153094400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J Rep Immunol"],"published-print":{"date-parts":[[2006,9]]},"abstract":"<jats:p><jats:bold>Problem\u2002<\/jats:bold> Endometriosis is the presence of ectopic uterine endometrial tissue in the peritoneal cavity. Peritoneal fluid samples of women with endometriosis show elevated interleukin\u20101 (IL\u20101)<jats:italic>\u03b2<\/jats:italic>, tumor necrosis factor (TNF)\u2010<jats:italic>\u03b1<\/jats:italic> and transforming growth factor (TGF)\u2010<jats:italic>\u03b2<\/jats:italic><jats:sub>1<\/jats:sub> levels, indicating that an altered immune system may play an important role in the pathogenesis of endometriosis. The invasion of ectopic endometrium into peritoneal mesothelium requires matrix metalloproteinases (MMPs) for tissue remodeling. Several MMPs are differentially expressed in human uterine endometrium with menstrual endometrium showing the highest level of expression. MMPs are stimulated by cytokines and also by the protein Extracellular Matrix Metalloproteinase Inducer (EMMPRIN).<\/jats:p><jats:p><jats:bold>Method of Study\u2002<\/jats:bold> To determine the role of cytokines in ectopic endometrial invasion, we investigated whether cytokines could regulate MMP production by endometrial fibroblast cells and whether this stimulation occurred through an effect on EMMPRIN expression. Human uterine fibroblasts (HUF) were treated with IL\u20101<jats:italic>\u03b2<\/jats:italic>, TGF\u2010<jats:italic>\u03b2<\/jats:italic><jats:sub>1<\/jats:sub> and TNF\u2010<jats:italic>\u03b1<\/jats:italic> in a dose dependent and time dependent manner (C, 0.1, 1, 10\u2003ng\/mL IL\u20101<jats:italic>\u03b2<\/jats:italic> or TGF\u2010<jats:italic>\u03b2<\/jats:italic><jats:sub>1<\/jats:sub>; C, 2, 10, 50\u2003ng\/mL TNF\u2010<jats:italic>\u03b1<\/jats:italic>) for 0, 6, 12, and 24\u2003hr. Cell conditioned medium samples were collected and concentrated at each timepoint for immunoblot analysis. Cellular RNA was collected for real time PCR analysis of MMPs\u20101, \u20102, \u20103 and EMMPRIN mRNA levels.<\/jats:p><jats:p><jats:bold>Results\u2002<\/jats:bold> Our results showed that IL\u20101<jats:italic>\u03b2<\/jats:italic> stimulated MMP\u20101 protein secretion and mRNA levels in a time dependent manner (<jats:italic>P<\/jats:italic>\u2003&lt;\u20030.05), MMP\u20102 mRNA in a time dependent manner and MMP\u20103 in a time and dose dependent manner. TNF\u2010<jats:italic>\u03b1<\/jats:italic> stimulated MMP\u20101 and \u20103 protein secretion in a time dependent manner and stimulated MMP\u20101, \u20102 and \u20103 mRNA levels in a time dependent manner (<jats:italic>P<\/jats:italic>\u2003&lt;\u20030.05). Neither IL\u20101<jats:italic>\u03b2<\/jats:italic> nor TNF\u2010<jats:italic>\u03b1<\/jats:italic> treatment affected MMP\u20102 protein secretion. TGF\u2010<jats:italic>\u03b2<\/jats:italic><jats:sub>1<\/jats:sub> inhibited MMP\u20101 and MMP\u20102 mRNAs at the highest treatment dose after 24\u2003hr but there was no effect on protein secretion. TGF\u2010<jats:italic>\u03b2<\/jats:italic><jats:sub>1<\/jats:sub> exerted no effect on MMP\u20103 mRNA or protein secretion (<jats:italic>P<\/jats:italic>\u2003&lt;\u20030.05). Neither of the cytokines affected EMMPRIN protein or mRNA levels but the 10\u2003ng\/mL TGF\u2010<jats:italic>\u03b2<\/jats:italic><jats:sub>1<\/jats:sub> treatment did cause a reduction in EMMPRIN mRNA levels.<\/jats:p><jats:p><jats:bold>Conclusions\u2002<\/jats:bold> These data show that elevated cytokines may play a role in the establishment of ectopic endometrium in the peritoneal cavity by stimulating MMPs to remodel the mesothelial lining of the peritoneum thus allowing for tissue invasion. The stimulation of MMPs by cytokines occurred without any change in EMMPRIN expression whereas the inhibitory effect of TGF\u2010<jats:italic>\u03b2<\/jats:italic><jats:sub>1<\/jats:sub> involved a reduction in EMMPRIN mRNA levels.<\/jats:p>","DOI":"10.1111\/j.1600-0897.2006.00418.x","type":"journal-article","created":{"date-parts":[[2006,7,17]],"date-time":"2006-07-17T11:21:10Z","timestamp":1153135270000},"page":"201-214","source":"Crossref","is-referenced-by-count":52,"title":["Cytokines Regulate Matrix Metalloproteinases in Human Uterine Endometrial Fibroblast Cells Through a Mechanism That Does Not Involve Increases in Extracellular Matrix Metalloproteinase Inducer"],"prefix":"10.1111","volume":"56","author":[{"given":"Andrea G.","family":"Braundmeier","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romana 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