Growth Factor Rescue of Cytokine Mediated Trophoblast Apoptosis

• DOI: 10.1053/plac.2001.0783
• Publication Date: 2002-07-26T11:24:48Z
• Authors: S. Smith; R. Francis; L. Guilbert; P.N. Baker
• Keywords: Platelet-Derived Growth Factor; Lymphokines; 0303 health sciences; Epidermal Growth Factor; Apoptosis; Cell Count; Endothelial Growth Factors; Pregnancy Proteins; Recombinant Proteins; Trophoblasts; Interferon-gamma; 03 medical and health sciences; Pregnancy; In Situ Nick-End Labeling; Humans; Intercellular Signaling Peptides and Proteins; Female; Fibroblast Growth Factor 2; Insulin-Like Growth Factor I; Growth Substances; Cells, Cultured; Placenta Growth Factor

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.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.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.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.