Role of tumor necrosis factor-alpha in the premature rupture of membranes and preterm labor pathways.
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.
Fortunato
Sephen J
SJ
Perinatal Research Center of the Women's Health Research and Education Foundation, Nashville, TN 37203, USA. fortunat@edge.net
Menon
Ramkumar
R
Lombardi
Salvatore J
SJ
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
D007375:Interleukin-1; D015850:Interleukin-6; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D014409:Tumor Necrosis Factor-alpha; D020780:Matrix Metalloproteinase 9