Regulation of Fas Ligand Expression by IL-8 in Human Endometrium

Numerous cytokines and growth factors are synthesized in the endometrium. IL-8 is one of these cytokines regulating endometrial function. It is a neutrophil chemoattractant/activating factor and a potent angiogenic agent. IL-8 is elevated in the peritoneal fluid of women with endometriosis. We have...

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Bibliographic Details
Published in:The journal of clinical endocrinology and metabolism 2002-08, Vol.87 (8), p.3921-3927
Main Authors: Selam, Belgin, Kayisli, Umit A, Garcia-Velasco, Juan A, Akbas, G Eda, Arici, Aydin
Format: Article
Language:English
Subjects:
Adult
Apoptosis - drug effects
Apoptosis - immunology
Biological and medical sciences
Endometriosis - immunology
Endometriosis - physiopathology
Endometrium - cytology
Endometrium - immunology
Fas Ligand Protein
fas Receptor - genetics
Female
Female genital diseases
Gene Expression - drug effects
Gene Expression - immunology
Gynecology. Andrology. Obstetrics
Humans
Interleukin-8 - pharmacology
Jurkat Cells
Medical sciences
Membrane Glycoproteins - genetics
Middle Aged
Non tumoral diseases
RNA, Messenger - analysis
Stromal Cells - cytology
Stromal Cells - physiology
T-Lymphocytes - cytology
T-Lymphocytes - physiology
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Summary:Numerous cytokines and growth factors are synthesized in the endometrium. IL-8 is one of these cytokines regulating endometrial function. It is a neutrophil chemoattractant/activating factor and a potent angiogenic agent. IL-8 is elevated in the peritoneal fluid of women with endometriosis. We have previously demonstrated a direct proliferative effect of IL-8 on endometrial stromal cells. We hypothesized that increased levels of IL-8 in the endometriotic environment could up- regulate Fas ligand (FasL) expression in endometrial cells and may be relevant for the development of a relative local immunotolerance in endometriosis by inducing apoptosis of cytotoxic T lymphocytes. To test our hypothesis, we studied the in vitro regulation of FasL expression and apoptosis by IL-8 in endometrial cells. Western blot analysis in endometrial stromal, glandular, and Ishikawa cells revealed that IL-8 up-regulated FasL protein expression in these cells. By semiquantitative RT-PCR analysis, IL-8 does not alter the expression of either Fas or FasL mRNA levels in these cells. Immunocytochemistry results from endometrial stromal cells treated with IL-8 demonstrated an up-regulation of FasL protein expression. IL-8 decreased apoptosis rate in endometrial stromal cells as evaluated by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling assay. We observed an increased apoptotic rate in Jurkat (T lymphocyte line) cells plated on endometrial stromal cells previously treated with IL-8. We speculate that increased FasL expression by IL-8 may induce apoptosis of T lymphocytes and thus produce a local immunotolerant environment for the development of ectopic implants.
ISSN:0021-972X
1945-7197
DOI:10.1210/jc.87.8.3921