title: Role of tumor necrosis factor-alpha in the premature rupture of membranes and preterm labor pathways.
abstract: OBJECTIVE
  To further delineate the differences between the preterm labor and premature rupture of the membrane pathways, we investigated the role of the inflammatory cytokines as activators of matrix metalloproteinases 2 and 9 in human fetal membranes.
  
  
  METHODS
  Normal amniochorionic membrane that is maintained in an organ explant system was stimulated with interleukin-1beta, tumor necrosis factor-alpha, or interleukin-6. The expression and activity of matrix metalloproteinases 2 and 9 in amniochorion was documented with reverse transcriptase-polymerase chain reaction and specific substrate activity assays. The matrix metalloproteinase inhibitor, tissue inhibitor of metalloproteinase-1, concentration was measured by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  Interleukin-1beta, tumor necrosis factor-alpha, and interleukin-6 induced the expression of matrix metalloproteinase-9 messenger RNA, whereas matrix metalloproteinase-2 expression was constitutive in control and cytokine-stimulated tissues. Matrix metalloproteinase-2 activity did not change after cytokine stimulation. Active matrix metalloproteinase-9 was significantly higher in tumor necrosis factor-stimulated tissues, which conversely were not changed after interleukin-1 or interleukin-6 stimulation. Tissue inhibitor of metalloproteinase-1 levels were decreased after interleukin-1 and tumor necrosis factor stimulation but changed after interleukin-6 stimulation.
  
  
  CONCLUSIONS
  Only tumor necrosis factor-alpha increases matrix metalloproteinase-9 activity in amniochorion.
authors.affiliation: Perinatal Research Center of the Women's Health Research and Education Foundation, Nashville, TN 37203, USA. fortunat@edge.net
authors.forename: Sephen J
authors.initials: SJ
authors.lastname: Fortunato
authors.forename: Ramkumar
authors.initials: R
authors.lastname: Menon
authors.forename: Salvatore J
authors.initials: SJ
authors.lastname: Lombardi
mesh_terms: D005260:Female; D005322:Premature Rupture of Fetal Membranes / Q000503:physiopathology*; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D007752:Obstetric Labor, Premature / Q000503:physiopathology*; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D007375:Interleukin-1; D015850:Interleukin-6; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D014409:Tumor Necrosis Factor-alpha; D020780:Matrix Metalloproteinase 9