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Endocrinology, doi:10.1210/en.2008-0264
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Endocrinology Vol. 150, No. 1 350-356
Copyright © 2009 by The Endocrine Society

Interleukin (IL)-1β Stimulates Migration and Survival of First-Trimester Villous Cytotrophoblast Cells through Endometrial Epithelial Cell-Derived IL-8

Yasushi Hirota, Yutaka Osuga, Akiko Hasegawa, Ako Kodama, Toshiki Tajima, Kahori Hamasaki, Kaori Koga, Osamu Yoshino, Tetsuya Hirata, Miyuki Harada, Yuri Takemura, Tetsu Yano, Osamu Tsutsumi and Yuji Taketani

Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, Tokyo 113-8655, Japan

Address all correspondence and requests for reprints to: Yutaka Osuga, M.D., Ph.D., Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. E-mail: yutakaos-tky{at}umin.ac.jp.

IL-1, secreted by human embryos and trophoblast cells, is important for successful implantation and pregnancy. We previously reported that IL-1β induced IL-8 production in human endometrial stromal cells (ESCs) and that induction was regulated by substances implicated in implantation. In the present study using human primary cells in culture, we measured IL-1β-induced production of IL-8 from endometrial epithelial cells (EECs) and ESCs and examined effects of the endometrium-derived IL-8 on migration and number of first-trimester villous cytotrophoblast cells (vCTs). Both basal and IL-1β-induced IL-8 levels of cell supernatants were much higher in EECs than ESCs. Addition of IL-1β to EECs increased the chemotactic activity of the supernatants to vCTs, and this effect was suppressed by immunoneutralization with anti-IL-8 antibody. Supernatants of IL-1β-stimulated EECs yielded significantly higher number of vCTs compared with those of untreated EECs, and the effect was inhibited by IL-8 antibody. These findings suggest that IL-1 promotes implantation by stimulating EECs to produce IL-8, which subsequently induces migration of vCTs and contributes to survival of vCTs.







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Copyright © 2009 by The Endocrine Society