Growth Factor Rescue of Cytokine Mediated Trophoblast Apoptosis
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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Apoptosis at the decidual/uterine interface allows initial separation of the maternal/placental unit at the time of parturition.
“putatively allowing for initial separation of the maternal/placental unit at the time of parturition40–43.”
From Conditional loss of ERK1 and ERK2 results in abnormal placentation and delayed parturition in the mouse (2019) · cites this paper as [40]
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- Authors
- Smith, S., Francis, R., Guilbert, L., & Baker, P. N.
- Affiliations
- University of Nottingham (GB)
- University of Alberta (CA)
- Venue
- Placenta
- Publisher
- Elsevier BV
- Published
- 2002-04
- Volume
- 23
- Issue
- 4
- Pages
- 322-330
- ISSN
- 0143-4004 (ISSN-L)
- OpenAlex
- W2068565307
- Cited by
- 90
- References
- 23
- Citations by year
- 2026: 1 · 2025: 3 · 2023: 4 · 2022: 3 · 2021: 3 · 2020: 3 · 2019: 3 · 2018: 4 · 2016: 4 · 2015: 3 · 2014: 5 · 2013: 2 · 2012: 2
- FWCI
- 2.19
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Placenta (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
- Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- trophoblast apoptosis, cytokine-induced apoptosis, TNF-α, interferon-gamma, basic fibroblast growth factor, insulin-like growth factor I, PDGF-AA, vascular endothelial growth factor, placental growth factor, epidermal growth factor, syncytiotrophoblast, cytotrophoblast, apoptosis inhibition
- MeSH terms
- Placenta Growth Factor, Cell Count, Cells, Cultured, Epidermal Growth Factor, Female, Growth Substances, Humans, Insulin-Like Growth Factor I, Interferon-gamma, Lymphokines, Platelet-Derived Growth Factor, Pregnancy, Pregnancy Proteins, Recombinant Proteins, Trophoblasts, Tumor Necrosis Factor-alpha, Fibroblast Growth Factor 2, Endothelial Growth Factors, Apoptosis, In Situ Nick-End Labeling, Intercellular Signaling Peptides and Proteins, Vascular Endothelial Growth Factors, Vascular Endothelial Growth Factor A
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