Interleukin-1beta-induced expression of IL-6 and production of human chorionic gonadotropin in human trophoblast cells via nuclear factor-kappaB activation.
OBJECTIVE
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-kappaB (NF-kappaB) during the induction of IL-6 by IL-1beta in human trophoblast cells.


METHODS
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-1beta (0-10 ng/mL), IL-1beta (10 ng/mL) together with IL-1 receptor antagonist (IL-1Ra) or NF-kappaB 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-1beta, were observed. The concentration of IL-6 was enhanced by IL-1beta in a dose-dependent fashion. The addition of IL-1Ra neutralized the effects of IL-1beta on IL-6 secretion. IL-1beta induced expression of phosphorylated IkappaB and the activation of NF-kappaB. The addition of TPCK reduced the IL-1beta-induced IL-6 expression. Adding IL-1beta increased beta-hCG production in a dose-dependent manner, and the addition of TPCK neutralized the effect of IL-1beta.


CONCLUSIONS
IL-1beta may induce the IL-6 expression and hCG production in human BeWo cells via NF-kappaB.
Tsukihara
Satoru
S
Department of Obstetrics and Gynecology, Tottori University School of Medicine, Yonago, Japan.
Harada
Tasuku
T
Deura
Imari
I
Mitsunari
Masahiro
M
Yoshida
Souichi
S
Iwabe
Tomio
T
Terakawa
Naoki
N
D015703:Antigens, CD / Q000235:genetics; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D006063:Chorionic Gonadotropin / Q000096:biosynthesis; D050822:Cytokine Receptor gp130; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics*; D008562:Membrane Glycoproteins / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000235:genetics; D019947:Receptors, Interleukin-6 / Q000235:genetics; D014327:Trophoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*
D015703:Antigens, CD; D006063:Chorionic Gonadotropin; D020672:I-kappa B Proteins; C494199:IL6ST protein, human; D007375:Interleukin-1; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D019947:Receptors, Interleukin-6; D050822:Cytokine Receptor gp130