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 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.
Selam
Belgin
B
Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology, Yale University School of Medicine, New Haven, Connecticut 06520-8063, USA.
Kayisli
Umit A
UA
Garcia-Velasco
Juan A
JA
Akbas
G Eda
GE
Arici
Aydin
A
D000328:Adult; D017209:Apoptosis / Q000187:drug effects* / Q000276:immunology; D004715:Endometriosis / Q000276:immunology / Q000503:physiopathology; D004717:Endometrium / Q000166:cytology* / Q000276:immunology; D053222:Fas Ligand Protein; D005260:Female; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D006801:Humans; D016209:Interleukin-8 / Q000494:pharmacology*; D019169:Jurkat Cells; D008562:Membrane Glycoproteins / Q000235:genetics*; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D017154:Stromal Cells / Q000166:cytology / Q000502:physiology; D013601:T-Lymphocytes / Q000166:cytology / Q000502:physiology; D019014:fas Receptor / Q000235:genetics
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D016209:Interleukin-8; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D019014:fas Receptor