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Estradiol administration controls eosinophilia through estrogen receptor-alpha activation during acute peritoneal inflammation.

Abstract : Estrogens influence the incidence and the course of numerous immune or inflammatory diseases in humans and in experimental models. For instance, estrogens prevent the accumulation of granulocytes in acute inflammatory murine models, but the respective actions on neutrophil and eosinophil trafficking remain to be clarified. We demonstrate here that in a model of TGC-induced sterile peritonitis in ovx mice, chronic E2 administration electively and strongly inhibited peritoneal eosinophil accumulation. E2 decreased BM eosinophil number, contributing to a marked prevention of the TGC-induced eosinophil blood mobilization. These effects on eosinophil mobilization and peritoneal accumulation were abolished in ER-α(-/-) mice, demonstrating the crucial role of this nuclear receptor. Grafting ER-α(-/-) mice with ER-α(+/+) BM cells restored the suppressive effect of E2 on peritoneal eosinophilia, although the action on eosinophil blood mobilization was still abrogated. We therefore explored additional mechanisms and found that E2 reduced the peritoneal concentrations of key eosinophil prosurvival factors (IL-5, IL-9, and IL-25) and enhanced eosinophil apoptosis during the inflammatory process. Furthermore, this proapoptotic effect of E2 was abrogated in IL-5-overexpressing Tg mice. To conclude, we demonstrate for the first time that ER-α activation by exogenous E2 administration strongly inhibits eosinophil accumulation during acute inflammation in a nonreproductive target site for estrogen through combined actions on eosinophil mobilization and apoptosis. This specific, suppressive effect of chronic E2 replacement therapy on eosinophils has to be integrated to further understand the evolution of eosinophil-associated diseases in menopausal women.
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Contributor : Marie Francoise Simon Connect in order to contact the contributor
Submitted on : Friday, August 19, 2011 - 3:19:11 PM
Last modification on : Monday, July 4, 2022 - 9:27:01 AM

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Victorine Douin-Echinard, Bertrand Calippe, Audrey Billon-Galès, Coralie Fontaine, Françoise Lenfant, et al.. Estradiol administration controls eosinophilia through estrogen receptor-alpha activation during acute peritoneal inflammation.. Journal of Leukocyte Biology, Society for Leukocyte Biology, 2011, 90 (1), pp.145-54. ⟨10.1189/jlb.0210073⟩. ⟨inserm-00615500⟩



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