Leptin regulation of the interleukin-1 system in human endometrial cells.
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-1beta (IL-1beta) up-regulates leptin and Ob-R, and both cytokines up-regulate beta3 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-1beta (0-3 nmol/l). Leptin stimulated IL-1 antagonist (IL-1Ra), IL-1beta secretion and expression of IL-1 receptor type I (IL-1R tI) in both cell types. IL-1beta 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-1beta on expression of the IL-1beta system and beta3 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-1beta 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.
Gonzalez
Ruben Rene
RR
Boston Biomedical Research Institute, 64 Grove Street, Watertown, MA 02472, USA. gonzalezr@bbri.org
Leary
Kristen
K
Petrozza
John Christopher
JC
Leavis
Paul Clifton
PC
D000906:Antibodies / Q000378:metabolism; D002478:Cells, Cultured; D004717:Endometrium / Q000166:cytology / Q000378:metabolism*; D005260:Female; D006801:Humans; D039661:Integrin beta3 / Q000378:metabolism; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000378:metabolism*; D020738:Leptin / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D054411:Receptors, Leptin; D012795:Sialoglycoproteins / Q000378:metabolism
D000906:Antibodies; C507763:IL1RN protein, human; D039661:Integrin beta3; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; C515448:LEPR protein, human; D020738:Leptin; D011956:Receptors, Cell Surface; D017472:Receptors, Interleukin-1; D054411:Receptors, Leptin; D012795:Sialoglycoproteins