[The role of matrix metalloproteinases for premature rupture of the membranes].

In order to investigate the correlation between premature rupture of the membrane (PROM) and chorioamnionitis, the effects of human tumor necrosis factor alpha (TNF alpha) and human interleukin-1 alpha (IL-1) on the production of matrix metalloproteinases (MMPs), tissue inhibitor of metalloproteinases (TIMP) and prostaglandin E2 (PGE2) in cultured human chorionic cells, were examined. The results were as follows: 1) TNF alpha enhanced the production of MMPs and PGE2 and suppressed TIMP production. 2) IL-1 stimulated the production of MMPs, TIMP and PGE2. 3) The combination of IL-1 and TNF alpha further augmented IL-1-induced production of MMPs, but IL-1-induced TIMP was suppressed by TNF alpha treatment. 4) At term, remarkable Type I collagenolytic activity was found in amniotic fluid from a patient with PROM complicated chorioamnionitis, whereas no collagenolytic activity was found in normal amniotic fluid. These results suggest that the degradation of extracellular matrix in fetal membranes with intraamniotic infection is caused by MMPs derived from chorionic cells through the inflammatory cytokines released in response to bacterial infection; PGE2 is released, causing uterine contraction. These effects combine to induce PROM.