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 facto r alpha (TNF), interleukin-1 alpha (IL-1 alpha), macrophage colony-stimulat ing factor (MCSF) and transforming growth factor beta (TGF beta) on the sec retion of matrix metalloproteinases (MMP), human chorionic gonadotrophin (H CG) and fetal fibronectin (fFN) by purified first trimester cytotrophoblast ic cells (CTB) in vitro. CTB were obtained from legal abortions and culture d in vitro in the presence or absence of the different cytokines. Secreted gelatinases were analysed in the culture supernatants by zymography, by mea surements of the total gelatinolytic activity and by enzyme immunoassays. H CG and fFN were measured by commercially available immunoassays. TNF increa sed the total gelatinolytic activity by increasing MMP-9 activity (P = 0.02 5-0.0177) but decreased MMP-2 activity (P < 0.03) and immunoreactivity (P < 0.05), fFN (P < 0.02) and HCG (P < 0.01). IL-1 alpha significantly increas ed the secretion of fFN (P < 0.02), the activity (P < 0.02) and immunoreact ivity (P < 0.05) of MMP-9 but had no effect on the other parameters. MCSF i ncreased MMP-9 immunoreactivity (P < 0.05) and moderately decreased HCG. TG F beta inhibited total gelatinolytic activity, MMP-9 activity and immunorea ctivity, but was without effect on MMP-2 concentrations and activity. TGF b eta decreased HCG (P < 0.041) and increased fFN (P < 0.042). Our results in dicate that TGF beta, TNF and IL-1 alpha are important regulators of tropho blastic MMP secretion.