Molecular Human Reproduction, Vol. 9, No. 3, 151-158,
March 2003
© 2003 European Society of Human Reproduction and Embryology
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Leptin regulation of the interleukin-1 system in human endometrial cells
Submitted on October 2, 2002; accepted on December 13, 2002
1 Boston Biomedical Research Institute, 64 Grove Street, Watertown, MA 02472, 2 Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, 3 Department of Physiology, Tufts University School of Medicine, Boston, MA 02111 and 4 Analytical Biotechnology Inc., 64 Grove Street, Watertown, MA 02472, USA
5 To whom correspondence should be addressed. e-mail: gonzalezr{at}bbri.org
We have previously shown that (i) leptin and leptin receptor (Ob-R) are expressed in the human endometrium, and (ii) leptin secretion is regulated in blastocyst and endometrial epithelial cell (EEC) co-cultures. Interleukin-1ß (IL-1ß) up-regulates leptin and Ob-R, and both cytokines up-regulate ß3 integrin expression in EEC. In the present investigation we examined the effect of leptin on the expression of the IL-1 system in EEC and endometrial stromal cells (ESC) cultured in a medium containing insulin, leptin or IL-1ß (0–3 nmol/l). Leptin stimulated IL-1 antagonist (IL-1Ra), IL-1ß secretion and expression of IL-1 receptor type I (IL-1R tI) in both cell types. IL-1ß and IL-1Ra secretion were down-regulated by IL-1R tI blockade using specific antibodies. Interestingly, leptin partially neutralized this effect. The blockade of Ob-R neutralized the effects of both leptin and IL-1ß on expression of the IL-1ß system and ß3 integrin and on phosphorylation of signal transducer and activator of transcription 3 (Stat3). These results suggest that leptin regulates the IL-1 system and that the blockade of functional Ob-R impairs leptin and IL-1ß functions at the endometrial level. Leptin could be an important molecule for implantation and a molecular mediator for actions of the IL-1 system. The fact that leptin, in the absence of IL-1, can trigger the expression of markers of endometrial receptivity and of the invasive trophoblast phenotype (as does IL-1), suggest that leptin could substitute for these IL-1 functions during the implantation process.
Key words: human endometrial cells/implantation/interleukin-1/leptin/leptin receptor
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