Effects of tumour necrosis factor-alpha, interleukin-1 alpha, macrophage colony stimulating factor and transforming growth factor beta on trophoblastic matrix metalloproteinases.

The aim of this study was to determine the effects of tumour necrosis factor alpha (TNF), interleukin-1 alpha (IL-1alpha), macrophage colony-stimulating factor (MCSF) and transforming growth factor beta (TGFbeta) on the secretion of matrix metalloproteinases (MMP), human chorionic gonadotrophin (HCG) and fetal fibronectin (fFN) by purified first trimester cytotrophoblastic cells (CTB) in vitro. CTB were obtained from legal abortions and cultured in vitro in the presence or absence of the different cytokines. Secreted gelatinases were analysed in the culture supernatants by zymography, by measurements of the total gelatinolytic activity and by enzyme immunoassays. HCG and fFN were measured by commercially available immunoassays. TNF increased the total gelatinolytic activity by increasing MMP-9 activity (P = 0.025-0.0177) but decreased MMP-2 activity (P < 0.03) and immunoreactivity (P < 0.05), fFN (P < 0.02) and HCG (P < 0.01). IL-1alpha significantly increased the secretion of fFN (P < 0.02), the activity (P < 0.02) and immunoreactivity (P < 0.05) of MMP-9 but had no effect on the other parameters. MCSF increased MMP-9 immunoreactivity (P < 0.05) and moderately decreased HCG. TGFbeta inhibited total gelatinolytic activity, MMP-9 activity and immunoreactivity, but was without effect on MMP-2 concentrations and activity. TGFbeta decreased HCG (P < 0.041) and increased fFN (P < 0.042). Our results indicate that TGFbeta, TNF and IL-1alpha are important regulators of trophoblastic MMP secretion.