Macrophage derived growth factors modulate Fas ligand expression in cultured endometrial stromal cells: a role in endometriosis.
Fas-Fas ligand (FasL) interactions play a significant role in the immune privilege status of certain cell populations, and several cytokines and growth factors can modulate their expression. When a FasL-expressing cell binds a Fas-bearing immune cell, it triggers its death by apoptosis. In this study, we demonstrate that normal human endometrial epithelial but not stromal cells express FasL. Moreover, we showed that macrophage-conditioned media induced FasL expression by endometrial stromal cells in a dose-dependent manner. To elucidate which macrophage product was responsible for the up-regulation of FasL, endometrial stromal cell cultures were treated with the macrophage products platelet-derived growth factor (PDGF), transforming growth factor (TGF)-beta1, and basic fibroblast growth factor (bFGF). The first two (which are known to be elevated in the peritoneal fluid of women with endometriosis) induced a dose-dependent up-regulation of FasL expression, which was specifically inhibited by the antibody. Interestingly, bFGF (which is not elevated in peritoneal fluid of women with endometriosis) did not induce any response. These results suggest that the pro-inflammatory nature of the peritoneal fluid of women with endometriosis induces the FasL expression by regurgitated endometrial cells, and signals Fas-mediated cell death of activated immune cells. This could be a mechanism for endometrial cells to escape immune surveillance, implant and grow.
Garcia-Velasco
J A
JA
Yale University School of Medicine, Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology, New Haven, CT 06520, USA.
Arici
A
A
Zreik
T
T
Naftolin
F
F
Mor
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D002454:Cell Differentiation; D002478:Cells, Cultured; D002822:Choriocarcinoma; D017077:Culture Media, Conditioned; D004717:Endometrium / Q000166:cytology* / Q000378:metabolism*; D053222:Fas Ligand Protein; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007951:Leukemia, Myeloid; D008024:Ligands; D008264:Macrophages / Q000502:physiology; D008562:Membrane Glycoproteins / Q000235:genetics*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011247:Pregnancy; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms
D017077:Culture Media, Conditioned; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008024:Ligands; D008562:Membrane Glycoproteins; D010982:Platelet-Derived Growth Factor; D016212:Transforming Growth Factor beta; D016222:Fibroblast Growth Factor 2