Progestin-inflammatory cytokine interactions affect matrix metalloproteinase-1 and-3 expression in term decidual cells: Implications for treatment of chorioamnionitis-induced preterm delivery

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dc.contributor.authorOner, Ceyda
dc.contributor.authorSchatz, Frederick
dc.contributor.authorKizilay, Gulnur
dc.contributor.authorMurk, William
dc.contributor.authorBuchwalder, Lynn F.
dc.contributor.authorKayisli, Umit A.
dc.contributor.authorArici, Aydin
dc.date.accessioned2024-06-12T11:19:28Z
dc.date.available2024-06-12T11:19:28Z
dc.date.issued2008
dc.departmentTrakya Üniversitesien_US
dc.description.abstractContext: Chorioamnionitis (CAM)-elicited preterm delivery (PTD) is associated with elevated amniotic fluid levels of IL-1 beta and TNF-alpha. We hypothesized that IL-1 beta and TNF-alpha may induce matrix metalloproteinase (MMP)-1 and MMP-3 activity to promote PTD by degrading decidual and fetal membranes and cervical extracellular matrix. Objective: Our objective was to evaluate: 1) MMP-1 and MMP-3 expression in decidual sections from uncomplicated term, idiopathic preterm, and CAM-complicated deliveries, and 2) the separate and interactive effects of IL-1 beta, TNF-alpha, medroxyprogesterone acetate (MPA), and a p38 MAPK inhibitor (SB203580) on MMP-1 and MMP-3 expression in term decidual cells (DCs). Interventions and Main Outcome Measures: Decidua were immunostained for MMP-1 and MMP-3. Cultured term DCs were incubated with estradiol (E2) or E2 plus MPA with or without IL-1 beta or TNF-alpha with or without S13203580. ELISA and Western blotting assessed secreted MMP-1 and MMP-3 levels, quantitative real-time RT-PCR assessed mRNA levels, and substrate gel zymography was used to determined MMP-1 and MMP-3 proteolytic activity. Results: MMP-1 and MMP-3 immunostaining was more prominent in CAM-complicated decidua vs. control preterm and term decidual specimens (P < 0.05). Compared with basal outputs by DCs incubated with E2, TNF-a enhanced MMP-1 and MMP-3 secretion by 14 +/- 3- and 9 +/- 2-fold, respectively, and IL-1 beta increased MMP-1 and MMP-3 secretion by 13 +/- 3- and 19 +/- 2-fold, respectively (P < 0.05). Addition of MPA lowered basal MMP-1 and MMP-3 outputs by 70%, whereas the TNF-alpha- and IL-1 beta-enhanced MMP-1 and MMP-3 levels were blunted by more than 50% (P < 0.05). SB203580 suppressed TNF-alpha- and IL-1 beta-induced MMP-1 and MMP-3 secretion by severalfold. Western blotting confirmed the ELISA results, and mRNA levels corresponded with MMP-1 and MMP-3 protein levels. MMP-1 and MMP-3 proteolytic activity was confirmed by substrate gel zymography. Conclusion: Augmented DC-expressed MMP-1 and MMP-3 in CAM-complicated pregnancies may promote PTD via decidual, fetal membrane, and cervical extracellular matrix degradation. Effects of progestin-p38 MAPK signaling inhibition on cytokine-enhanced MMP-1 and MMP-3 expression in term DCs suggest alternative mechanisms to prevent CAM-induced PTD.en_US
dc.description.sponsorshipNHLBI NIH HHS [R01 HL070004, 1 R01 HL070004-04] Funding Source: Medline; NICHD NIH HHS [R01 HD033937, 2R01HD33937-05] Funding Source: Medlineen_US
dc.identifier.doi10.1210/jc.2007-1538
dc.identifier.endpage259en_US
dc.identifier.issn0021-972X
dc.identifier.issn1945-7197
dc.identifier.issue1en_US
dc.identifier.pmid17940116en_US
dc.identifier.scopus2-s2.0-38149014612en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.startpage252en_US
dc.identifier.urihttps://doi.org/10.1210/jc.2007-1538
dc.identifier.urihttps://hdl.handle.net/20.500.14551/25201
dc.identifier.volume93en_US
dc.identifier.wosWOS:000252359400044en_US
dc.identifier.wosqualityQ1en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherEndocrine Socen_US
dc.relation.ispartofJournal Of Clinical Endocrinology & Metabolismen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectNecrosis-Factor-Alphaen_US
dc.subjectFactor-Kappa-Ben_US
dc.subjectPremature Ruptureen_US
dc.subjectClinical-Significanceen_US
dc.subjectGene-Expressionen_US
dc.subjectAmniotic-Fluiden_US
dc.subjectInterleukin-1-Betaen_US
dc.subjectStromelysinen_US
dc.subjectActivationen_US
dc.subjectMembranesen_US
dc.titleProgestin-inflammatory cytokine interactions affect matrix metalloproteinase-1 and-3 expression in term decidual cells: Implications for treatment of chorioamnionitis-induced preterm deliveryen_US
dc.typeArticleen_US

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