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Epidermal growth factor inhibits cytokine‐induced apoptosis of primary human trophoblasts
Author(s) -
GarciaLloret Maria Ines,
Yui Jane,
WinklerLowen Bonnie,
Guilbert Larry J.
Publication year - 1996
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/(sici)1097-4652(199605)167:2<324::aid-jcp17>3.0.co;2-7
Subject(s) - syncytiotrophoblasts , epidermal growth factor , trophoblast , cytokine , biology , tumor necrosis factor alpha , apoptosis , placenta , endocrinology , microbiology and biotechnology , programmed cell death , medicine , cancer research , cell culture , immunology , fetus , pregnancy , biochemistry , genetics
In the placenta, as in other organs, the development and maintenance of the differentiated phenotype depend on a balance between cell proliferation, maturation, and death. We are interested in the mechanisms that regulate the survival and differentiation of placental trophoblasts and have recently demonstrated that the inflammatory cytokines tumor necrosis factor alpha (TNFα) and gamma interferon (IFNγ) act in concert to induce apoptotic cell death in normal cytotrophoblasts in culture. In this report we show that exposure to epidermal growth factor (EGF), a 6,700 dalton polypeptide that is abundantly expressed in maternal and fetal tissues, blocks the in vitro TNF/IFN‐induced cytotoxicity of human cytotrophoblasts and syncytiotrophoblasts from normal term placentas. This antagonistic effect is dose‐related (10 −10 M EGF, half‐maximal) and proceeds via the interruption of an early step in the cytokine‐induced apoptotic response. These observations suggest a novel role for EGF in normal placental development and indicate that the interplay between EGF, TNFα, and IFNγ may determine the rate of trophoblast growth and renewal during gestation. © 1996 Wiley‐Liss, Inc.