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

Belgin Selam
In: Journal of Clinical Endocrinology & Metabolism · 2002 · vol. 87(8) , pp. 3921–3927 · doi:10.1210/jc.87.8.3921 · W4238977351
article OA: bronze CC0 ⤵ 10 in-corpus citations
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This study found that IL-8 up-regulates Fas ligand protein expression in human endometrial cells, leading to decreased endometrial stromal cell apoptosis but increased Jurkat cell apoptosis, potentially contributing to local immune tolerance in endometriosis.

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Abstract

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.(

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endometriosis

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