Progestin-Inflammatory Cytokine Interactions Affect Matrix Metalloproteinase-1 and -3 Expression in Term Decidual Cells: Implications for Treatment of Chorioamnionitis-Induced Preterm Delivery
Autor: | Aydin Arici, Gulnur Kizilay, Charles J. Lockwood, Umit A. Kayisli, Lynn Buchwalder, Frederick Schatz, Ceyda Oner, William Murk |
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Jazyk: | angličtina |
Rok vydání: | 2007 |
Předmět: |
Matrix Metalloproteinase 3
medicine.medical_specialty Amniotic fluid Pyridines Endocrinology Diabetes and Metabolism medicine.medical_treatment Clinical Biochemistry Blotting Western Interleukin-1beta Context (language use) Enzyme-Linked Immunosorbent Assay Medroxyprogesterone Acetate Biology Matrix metalloproteinase Chorioamnionitis Biochemistry Endocrinology Obstetric Labor Premature Pregnancy Internal medicine medicine Decidua Humans Decidual cells RNA Messenger Protein Kinase Inhibitors Progesterone Congeners Reverse Transcriptase Polymerase Chain Reaction Tumor Necrosis Factor-alpha Biochemistry (medical) Imidazoles medicine.disease Immunohistochemistry medicine.anatomical_structure Cytokine Original Article Female Matrix Metalloproteinase 1 |
Popis: | Context: Chorioamnionitis (CAM)-elicited preterm delivery (PTD) is associated with elevated amniotic fluid levels of IL-1β and TNF-α. We hypothesized that IL-1β and TNF-α 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-1β, TNF-α, 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-1β or TNF-α with or without SB203580. 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-α enhanced MMP-1 and MMP-3 secretion by 14 ± 3- and 9 ± 2-fold, respectively, and IL-1β 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-α- and IL-1β-enhanced MMP-1 and MMP-3 levels were blunted by more than 50% (P < 0.05). SB203580 suppressed TNF-α- and IL-1β-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. |
Databáze: | OpenAIRE |
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