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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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