title: Interleukin (IL)-1beta stimulates migration and survival of first-trimester villous cytotrophoblast cells through endometrial epithelial cell-derived IL-8.
abstract: IL-1, secreted by human embryos and trophoblast cells, is important for successful implantation and pregnancy. We previously reported that IL-1beta 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-1beta-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-1beta-induced IL-8 levels of cell supernatants were much higher in EECs than ESCs. Addition of IL-1beta 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-1beta-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.
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, 7-3-1, Hongo, Tokyo 113-8655, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Hirota
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Osuga
authors.forename: Akiko
authors.initials: A
authors.lastname: Hasegawa
authors.forename: Ako
authors.initials: A
authors.lastname: Kodama
authors.forename: Toshiki
authors.initials: T
authors.lastname: Tajima
authors.forename: Kahori
authors.initials: K
authors.lastname: Hamasaki
authors.forename: Kaori
authors.initials: K
authors.lastname: Koga
authors.forename: Osamu
authors.initials: O
authors.lastname: Yoshino
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hirata
authors.forename: Miyuki
authors.initials: M
authors.lastname: Harada
authors.forename: Yuri
authors.initials: Y
authors.lastname: Takemura
authors.forename: Tetsu
authors.initials: T
authors.lastname: Yano
authors.forename: Osamu
authors.initials: O
authors.lastname: Tsutsumi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Taketani
mesh_terms: D000328:Adult; D018929:Cell Culture Techniques; D002465:Cell Movement / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects*; D004717:Endometrium / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology*; D016209:Interleukin-8 / Q000494:pharmacology; D016906:Interleukin-9 / Q000502:physiology*; D008875:Middle Aged; D011247:Pregnancy; D011261:Pregnancy Trimester, First
chemical_list: D053583:Interleukin-1beta; D016209:Interleukin-8; D016906:Interleukin-9