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  • Title: Growth factor rescue of cytokine mediated trophoblast apoptosis.
    Author: Smith S, Francis R, Guilbert L, Baker PN.
    Journal: Placenta; 2002 Apr; 23(4):322-30. PubMed ID: 11969343.
    Abstract:
    INTRODUCTION: Apoptosis can be induced in cytotrophoblasts and syncytiotrophoblast in culture by a combination of TNF-alpha and IFN-gamma (Yui et al., 1994a; Garcia-Lloret et al., 1996). This apoptotic action of TNF-alpha and IFN-gamma can be inhibited/'rescued' by EGF (Garcia-Lloret et al., 1996). Additional 'survival' factors have been sought which might protect cells against apoptosis induced by TNF-alpha/IFN-gamma. The survival factors investigated were bFGF, IGF-1, PDGF-AA, VEGF and PLGF. These cytokines were chosen specifically because in common with EGF, the receptors for these molecules are all direct protein tyrosine kinases. MATERIALS AND METHODS: All the experiments were carried out using a standard cell culture protocol (Yui et al., 1994a, b; Garcia-Lloret et al., 1996). Apoptosis was induced using TNF-alpha/IFN-gamma, and rescue was attempted using the various cytokines. Apoptosis was identified using the TUNEL technique and quantified by counting 3000 cells in each experimental well. RESULTS: As in previous studies EGF produced a complete inhibition of the apoptotic action of TNF-alpha/IFN-gamma. bFGF, IGF-1, and PDGF-AA produced a partial but significant inhibition of the apoptotic action of TNF-alpha/IFN-gamma. VEGF and PLGF in these experiments had no protective effects against TNF-alpha/IFN-gamma induced apoptosis. DISCUSSION: Previous studies relating to EGF have been confirmed. bFGF, IGF-1, and PDGF have all been shown to provide partial protection against TNF-alpha/IFN-gamma induced apoptosis. VEGF and PLGF did not protect against apoptosis, and the mechanisms of action remain unclear.
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