Trophoblast-derived transforming growth factor-beta 1 suppresses cytokine-induced, but not gonadotropin-releasing hormone-induced, release of human chorionic gonadotropin by normal human trophoblasts.
Using a transforming growth factor-beta (TGF beta)-sensitive cell line, Mv1Lu (or CCL 64), we demonstrated that trophoblasts predominantly produced a latent form of TGF beta. After converting latent TGF beta to active TGF beta in vitro by acid (pH 2.5), alkali (pH 10.0), or heat (90 C; 10 min) treatment, addition of rabbit anti-TGF beta 1 antiserum resulted in the elimination of TGF beta activity, thus suggesting that trophoblasts produced at least a certain amount of latent TGF beta 1. To investigate the role of TGF beta 1 in placental hormonogenesis, we first studied the effect of recombinant (r) TGF beta 1 on the production of interleukin-6 (IL-6) and hCG by trophoblasts. rTGF beta 1 exerted no inhibitory activity on IL-6 and hCG production. The effect of rTGF beta 1 on cytokine-induced IL-6 and hCG release was then examined. While rTGF beta 1 failed to inhibit basal hCG secretion, it did inhibit recombinant tumor necrosis factor-alpha (rTNF alpha)-induced IL-6 release as well as rTNF alpha- and rIL-6-induced hCG release in a dose-dependent manner. However, rIL-1 alpha-induced IL-6 and hCG release was remarkably sensitive to rTGF beta 1-mediated suppression. In contrast, GnRH-induced hCG release, the response of which is independent of the IL-6 and IL-6 receptor system in trophoblasts, was completely resistant to rTGF beta 1. Thus, trophoblast-derived TGF beta 1 is an important regulatory molecule of cytokine-dependent, but not cytokine-independent, hCG release, possibly by converting latent TGF beta to active TGF beta at the local site of trophoblasts.
Matsuzaki
N
N
Department of Obstetrics and Gynecology, Osaka University Medical School, Japan.
Li
Y
Y
Masuhiro
K
K
Jo
T
T
Shimoya
K
K
Taniguchi
T
T
Saji
F
F
Tanizawa
O
O
D006063:Chorionic Gonadotropin / Q000378:metabolism*; D016207:Cytokines / Q000494:pharmacology*; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology*; D006801:Humans; D007375:Interleukin-1 / Q000037:antagonists & inhibitors; D015850:Interleukin-6 / Q000378:metabolism; D011994:Recombinant Proteins; D012016:Reference Values; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000494:pharmacology*; D014327:Trophoblasts / Q000737:chemistry / Q000378:metabolism*
D006063:Chorionic Gonadotropin; D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D007987:Gonadotropin-Releasing Hormone