Molecular Human Reproduction, Vol. 8, No. 12, 1096-1102,
December 2002
© 2002 European Society of Human Reproduction and Embryology
Molecular events in the uterus |
Endometrial interleukin-6 in vitro is not regulated directly by female steroid hormones, but by pro-inflammatory cytokines and hypoxia
1 Department of Endocrinology and Reproductive Medicine, Universitätsklinikum Heidelberg, Voßstraße 9, 69115 Heidelberg, Germany and 2 Department of Obstetrics and Gynaecology, Klinikum der Universitaet Muenchen-Grosshadern, Marchioninistraße 15, 81377 Muenchen, Germany
Abstract
Endometrial interleukin-6 (IL-6) mRNA has been reported to be suppressed in the mid-secretory phase in patients with recurrent early spontaneous abortions. This prompted our study concerning the regulation of endometrial IL-6 in cell culture models of endometrial epithelial and stromal cells. Steroid-dependent secretion of IL-6 was analysed by 17ß-estradiol (10-8 mol/l) or progesterone (10-6 mol/l) treatment and withdrawal (n = 8). Regulation by pro-inflammatory cytokines was studied in co-cultures of endometrial cells with human blood peripheral mononuclear cells (PBMC; n = 5) and by stimulation with IL-1ß, IL-6 and tumour necrosis factor 
(TNF), secreted by PBMCs at high concentrations. Regulation by hypoxia was assessed by culture of endometrial cells in 2% oxygen for 6 and 24 h (n = 5). IL-6 mRNA and protein levels were analysed by RT–PCR and enzyme-linked immunosorbent assays respectively. Endometrial IL-6 was not directly affected by 17ß-estradiol and/or progesterone. Co-culturing endometrial cells with PBMCs led to an increase of stromal but not epithelial IL-6 mRNA levels. In stromal cells, IL-6 secretion increased 2–10-fold if stimulated with 10 ng/ml recombinant IL-1ß or TNF (P < 0.05). Hypoxia stimulated IL-6 secretion in epithelial cells up to 2-fold and in stromal cells up to 48-fold (P < 0.05). In conclusion, IL-6 expression in stromal and epithelial cells in vitro is regulated differently by pro-inflammatory cytokines and hypoxia. These results suggest a tight and specific network of control for this important cytokine within different endometrial compartments.
cytokines/endometrium/hypoxia/interleukin-6/steroids
Notes
3 To whom correspondence should be addressed. E-mail: michael.von.wolff{at}med.uni-heidelberg.de
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