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.

STUDY DESIGN:

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.

CONCLUSION:

Only tumor necrosis factor-alpha increases matrix metalloproteinase-9 activity in amniochorion.

• Authors: Sephen J Fortunato, Ramkumar Menon, Salvatore J Lombardi
• Journal: American journal of obstetrics and gynecology (Am J Obstet Gynecol) Vol. 187 Issue 5 Pg. 1159-62 (Nov 2002) ISSN: 0002-9378 [Print] United States
• PMID: 12439495 (Publication Type: Journal Article)

Chemical References

• Interleukin-1
• Interleukin-6
• RNA, Messenger
• Tissue Inhibitor of Metalloproteinase-1
• Tumor Necrosis Factor-alpha
• Matrix Metalloproteinase 9

Topics

• Female
• Fetal Membranes, Premature Rupture (physiopathology)
• Humans
• In Vitro Techniques
• Interleukin-1 (pharmacology)
• Interleukin-6 (pharmacology)
• Matrix Metalloproteinase 9 (genetics)
• Obstetric Labor, Premature (physiopathology)
• Pregnancy
• RNA, Messenger (metabolism)
• Tissue Inhibitor of Metalloproteinase-1 (metabolism)
• Tumor Necrosis Factor-alpha (metabolism, pharmacology)