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

Abstract

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