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

Abstract

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.