Growth factor rescue of cytokine mediated trophoblast apoptosis.
BACKGROUND
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.


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.


CONCLUSIONS
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.
Smith
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Department of Obstetrics, Gynaecology and Midwifery, School of Human Development, City Hospital, University of Nottingham, Nottingham, UK.
Francis
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Guilbert
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Baker
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PN
D017209:Apoptosis / Q000187:drug effects*; D002452:Cell Count; D002478:Cells, Cultured; D016228:Endothelial Growth Factors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D020287:In Situ Nick-End Labeling; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology*; D008222:Lymphokines / Q000494:pharmacology; D000072483:Placenta Growth Factor; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000494:pharmacology; D011994:Recombinant Proteins; D014327:Trophoblasts / Q000166:cytology* / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; C000608036:PGF protein, human; D010982:Platelet-Derived Growth Factor; D011257:Pregnancy Proteins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C075278:platelet-derived growth factor A; D016222:Fibroblast Growth Factor 2; D000072483:Placenta Growth Factor; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I; D007371:Interferon-gamma