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,
ERIKO NISHINO,
TAKESHI TANIGUCHI,
TAKASHI KAMEDA,
YING LI,
FUMITAKA SAJI and
OSAMU TANIZAWA
Department of Obstetrics and Gynecology, Osaka University Medical School 1–1–50, Fukushima, Fukushima-ku, Osaka 553, Japan
Interleukin-1 (IL-1) has a unique activity to stimulate the release of multiple hormones in a number of human and murine endocrine systems. IL-6 also expresses such activities by activating IL-6-receptor (R)-mediated signal transduction pathways. Since the placenta produces both of these cytokines and endocrine hormones such as hCG, we investigated how these cytokines regulate hCG release by normal trophoblasts. Trophoblasts purified by Percoll density gradient released hCG from 120 min after stimulation with recombinant (r) IL-1
, and its release was dependent on the rIL-1 concentration used. The rIL-1-stimulated trophoblasts released a molecule with IL-6 activity antecedently, as determined by an IL-6-dependent cell line, MH60.BSF2 cells. The IL-6 identity of the released molecule was confirmed by goat anti-IL-6 antiserum. rIL-1-mediated hCG release from trophoblasts was completely abrogated to the basal level by pretreatment of the trophoblasts with PMl, an anti-IL-6-R monoclonal antibody. Identical results were observed with rIL-1β. These results showed that rIL-1-induced hCG release was totally dependent on IL-6- and IL-6-R-mediated signal transduction in human trophoblasts. The presence of peripheral monocytes in the purified trophoblast fraction, however, induced a rapid decrease in IL-6 and hCG release after their maximal release, suggesting some regulatory interaction between trophoblasts and the monocytes.
In contrast, rIL-1-mediated enhancement of IL-6 and hCG secretion by purified trophoblasts was no longer observed at 24 h compared with that of the unstimulated trophoblasts, while spontaneous hCG secretion was significantly inhibited by pretreatment of trophoblasts with PMl. The results showed that IL-6 and hCG secretion might also be regulated by a number of agents besides IL-1, and that hCG secretion as well as its release is dependent on IL-6 and IL-6-R system in trophoblasts.
* This work was supported by Grants-in-Aid for Scientific Research (02454382, 63570779, 63480367, and 01570930) from the Ministry of Education, Science, and Culture (Tokyo, Japan).
To whom all correspondence and requests for reprints should be addressed.
Received June 1, 1990.
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