TUMOR-NECROSIS-FACTOR-ALPHA STIMULATES THE BIOSYNTHESIS OF MATRIX METALLOPROTEINASES AND PLASMINOGEN-ACTIVATOR IN CULTURED HUMAN CHORIONIC CELLS

To investigate the role of tumor necrosis factor-alpha (TNF-alpha) in advanced collagenolysis and degradation of connective tissue components in preterm parturition, the effects of human recombinant TNF-alpha (hrTNF-alpha) on the production of matrix metalloproteinase 1 (MMP-1)/tissue collagenase, MMP-3/stromelysin, tissue inhibitor of metalloproteinases (TIMP), urokinase type-plasminogen activator (uPa) and prostaglandin (PG) E2 in human chorionic cells were examined in vitro. Human chorionic cells, but not amniotic cells, were found to respond to macrophage-conditioned medium (contains mainly interleukin 1) to produce MMP-1 and MMP-3. This indicated that the chorionic cell is one of the MMP-producing cells of fetal membranes. When confluent chorionic cells were treated with hrTNF-alpha, the production of MMP-1 and MMP-3 as well as of uPa and PGE2 was greatly increased in a dose-dependent manner. In contrast, the production of TIMP was suppressed by hrTNF-alpha. These results suggested that TNF-alpha may participate in destruction of collagen and other connective tissue matrix components of fetal membranes and in promotion of uterine contractility in preterm parturition with intraamniotic infection.