Interleukin (IL)-1beta stimulates migration and survival of first-trimester villous cytotrophoblast cells through endometrial epithelial cell-derived IL-8.
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.
Hirota
Yasushi
Y
Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, 7-3-1, Hongo, Tokyo 113-8655, Japan.
Osuga
Yutaka
Y
Hasegawa
Akiko
A
Kodama
Ako
A
Tajima
Toshiki
T
Hamasaki
Kahori
K
Koga
Kaori
K
Yoshino
Osamu
O
Hirata
Tetsuya
T
Harada
Miyuki
M
Takemura
Yuri
Y
Yano
Tetsu
T
Tsutsumi
Osamu
O
Taketani
Yuji
Y
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
D053583:Interleukin-1beta; D016209:Interleukin-8; D016906:Interleukin-9