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Submitted on September 13, 2004
Accepted on December 9, 2004
Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, CT, 06520 USA. Department of Histology and Embryology, Akdeniz University School of Medicine, Antalya, 07070 Turkey. Department of Pathology, Yale University School of Medicine, New Haven, CT, 06520 USA. Ege University School of Medicine Department of Obstetrics and Gynecology, Bornova, Izmir 35100, Turkey, Dokuz Eylul University School of Medicine, Department of Pathology, Inciralti, Izmir, 35340, Turkey
* To whom correspondence should be addressed. E-mail: aydin.arici{at}yale.edu.
The elevation of the pro-inflammatory chemoattractant cytokine levels in ectopic and eutopic endometrium of endometriosis implies an inflammatory basis for this disease. The relationship between endothelial cells and leukocytes is likely to be important in the regulation of inflammatory mediators of endometriosis. The aim of this study is to describe the temporal and spatial expression of interleukin-8 (IL-8) in human endometrial endothelial cells (HEEC) in vivo and to compare the in vitro regulation of IL-8 expression by sex steriods in HEEC from women with or without endometriosis. Eutopic endometrial tissues and endometriosis implants were grouped according to menstrual cycle phase and examined by immunohistochemistry for IL-8 expression. Endothelial cells of endometriotic implants expressed higher IL-8 immunoreactivity compared with endothelial cells of eutopic endometrium of women with or without endometriosis (P < 0.02). For in vitro studies, HEEC were isolated from women with or without endometriosis and was grown to pre-confluence. The purity of cultured HEEC (90-95%) was confirmed by immunocytochemistry using endothelium-specific markers CD31 and CD146. The effects of estradiol (5 x 10-8M), progesterone (10-7M), or both, on IL-8 mRNA and protein levels were analyzed by RT-PCR and ELISA, respectively. Sex steroids reduced the expression of IL-8 mRNA and protein in HEEC from women without endometriosis. On the other hand, both estradiol and progesterone stimulated IL-8 mRNA and protein expression in HEEC from women with endometriosis. We postulate that the stimulation of chemokine expression by sex steroids in HEEC of women with endometriosis may play a role in the inflammatory aspect of this disease.
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