Mol. Hum. Reprod. Advance Access published online on October 27, 2005
Molecular Human Reproduction, doi:10.1093/molehr/gah233
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1 Department of Obstetrics & Gynecology, University of Florida College of Medicine, Gainesville, FL, USA
* To whom correspondence should be addressed. Based on the endometrial spatial and temporal expression of interleukins (ILs) IL-13 and IL-15 during the normal menstrual cycle, we hypothesized that ovarian steroids and non-steroidal factors regulate their expression in a cell-specific manner. To test this hypothesis and determine IL-13/IL-15 actions, we used endometrial epithelial (EEC) and stromal (ESC) cells isolated and cultured under defined conditions. We confirmed the expression of IL-13 and IL-15 in these cells and further demonstrated that 17
Article
Differential regulation of interleukins IL-13 and IL-15 by ovarian steroids, TNF-
and TGF-
in human endometrial epithelial and stromal cells
2 Department of Obstetrics & Gynecology, University of Florida College of Medicine, Gainesville, FL, USA.
Nasser Chegini, E-mail: cheginin{at}obgyn.ufl.edu
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Abstract
estradiol (E2), medroxyprogesterone acetate (MPA) and their combination differentially regulated their mRNA expression and protein production in a time- and cell-specific manner (P < 0.05). We also showed that tumour necrosis factor-
(TNF-
; 10 and 25 ng/ml) and transforming growth factor-
(TGF-
; 1 and 5 ng/ml), cytokines with inflammatory and immune regulatory functions in a cell- and dose-dependent manner regulate the expression of IL-13 and IL-15 (P < 0.05). Functionally, IL-13 and IL-15 1-100 ng/ml displayed a limited mitogenic activity towards EEC and ESC; however, they regulated the expression of TNF receptor type 1 (TNFR) mRNA and soluble protein in a cell-specific manner (P < 0.05). We conclude that ovarian steroids, TNF-
and TGF-
act as key regulators of endometrial IL-13 and IL-15 expression which act locally regulating TNFR expression in a cellspecific manner. Based on these findings, we conclude that IL-13/IL-15, either alone or through their interactions with other cytokines, influence the outcome of endometrial inflammatory/immune responses during the normal menstrual cycle, and due to their altered expression may extend these processes in dysfunctional bleeding and endometriosis.
/TNF-
.
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