Cytotoxic effects of tumour necrosis factor (TNF)-alpha and interferon-gamma on cultured human trophoblast are modulated by fibronectin

Tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma, produced by maternal inflammatory cells, may compromise trophoblast survival at the tro phoblast-maternal interface and notably in the placental bed which is invad ed by trophoblast. Extracellular matrix components, e.g. fibronectin, may e nhance trophoblast survival. A possible protective effect of fibronectin ag ainst toxic effects of TNF-alpha and IFN-gamma was investigated in cultured trophoblasts isolated from six human term placentas, grown on uncoated and fibronectin-coated plastics. IFN-gamma and increasing doses of TNF-alpha r esulted in decreasing viability of trophoblast on uncoated as well as fibro nectin-coated dishes, as shown by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assays, but for each TNF/IFN treatment condition viability on fibronectin was higher (P < 0.001). Epidermal growth factor ( EGF), a growth factor reported to protect against TNF-alpha/IFN-gamma induc ed toxicity, resulted in further increased viability, but not if IFN-gamma was included in the treatment. EGF caused increased fibronectin secretion i nto the medium (P < 0.001), and double cytokeratin/fibronectin immunostaini ng confirmed the trophoblastic nature of fibronectin secreting cells. We co nclude that fibronectin increases viability, but does not completely abolis h the cytotoxic action of TNF-alpha and IFN-gamma on trophoblast. The prote ctive effect of EGF may be related to stimulation of fibronectin secretion by trophoblast.