Interleukin-1β-induced Expression of IL-6 and Production of Human Chorionic Gonadotropin in Human Trophoblast Cells via Nuclear Factor-κB Activation


Address reprint requests to Tasuku Harada, Department of Obstetrics and Gynecology, Tottori University School of Medicine, Yonago 683-8504, Japan.


Problem:  The cytokine, interleukin-6 (IL-6), stimulates the production of human chorionic gonadotropine (hCG) in chorionic cells. The purpose of this study was to examine the role of nuclear factor-κB (NF-κB) during the induction of IL-6 by IL-1β in human trophoblast cells.

Method of study:  Reverse transcription-polymerase chain reaction was used to determine the gene expressions of IL-1, IL-1 receptor (IL-1R), IL-6R and gp130 in a human choriocarcinoma cell line, BeWo. The BeWo cells were cultured for 24 hr with IL-1β (0–10 ng/mL), IL-1β (10 ng/mL) together with IL-1 receptor antagonist (IL-1Ra) or NF-κB inhibitor, N-tocyl-l-phenylalanine chloromethyl ketone (TPCK). The concentrations of IL-6 in culture supernatants were measured by enzyme-linked immunosorbent assay.

Results:  The gene expressions of IL-1R, IL-6R and gp130, but not IL-1β, were observed. The concentration of IL-6 was enhanced by IL-1β in a dose-dependent fashion. The addition of IL-1Ra neutralized the effects of IL-1β on IL-6 secretion. IL-1β induced expression of phosphorylated IκB and the activation of NF-κB. The addition of TPCK reduced the IL-1β-induced IL-6 expression. Adding IL-1β increased β-hCG production in a dose-dependent manner, and the addition of TPCK neutralized the effect of IL-1β.

Conclusion:  IL-1β may induce the IL-6 expression and hCG production in human BeWo cells via NF-κB.