Role of tumor necrosis factor-α in the premature rupture of membranes and preterm labor pathways

Stephen J. Fortunato, Ramkumar Menon, Salvatore J. Lombardi

Research output: Contribution to journalArticlepeer-review

114 Scopus citations


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. STUDY DESIGN: Normal amniochorionic membrane that is maintained in an organ explant system was stimulated with interleukin-1β, tumor necrosis factor-α, 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-1β, tumor necrosis factor-α, 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. CONCLUSION: Only tumor necrosis factor-α increases matrix metalloproteinase-9 activity in amniochorion.

Original languageEnglish (US)
Pages (from-to)1159-1162
Number of pages4
JournalAmerican journal of obstetrics and gynecology
Issue number5
StatePublished - Nov 2002
Externally publishedYes


  • Amniochorion
  • Cytokine
  • Matrix metalloproteinase
  • Premature rupture of membranes
  • Preterm labor

ASJC Scopus subject areas

  • Obstetrics and Gynecology


Dive into the research topics of 'Role of tumor necrosis factor-α in the premature rupture of membranes and preterm labor pathways'. Together they form a unique fingerprint.

Cite this