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

Tumour necrosis factor (TNF)-α and interferon (IFN)-γ, produced by maternal inflammatory cells, may compromise trophoblast survival at the trophoblast–maternal interface and notably in the placental bed which is invaded by trophoblast. Extracellular matrix components, e.g. fibronectin, may enhance trophoblast survival. A possible protective effect of fibronectin against toxic effects of TNF-α and IFN-γ was investigated in cultured trophoblasts isolated from six human term placentas, grown on uncoated and fibronectin-coated plastics. IFN-γ and increasing doses of TNF-α resulted in decreasing viability of trophoblast on uncoated as well as fibronectin-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-α/IFN-γ induced toxicity, resulted in further increased viability, but not if IFN-γ was included in the treatment. EGF caused increased fibronectin secretion into the medium (P < 0.001), and double cytokeratin/fibronectin immunostaining confirmed the trophoblastic nature of fibronectin secreting cells. We conclude that fibronectin increases viability, but does not completely abolish the cytotoxic action of TNF-α and IFN-γ on trophoblast. The protective effect of EGF may be related to stimulation of fibronectin secretion by trophoblast.