Masuhiro K, Matsuzaki N, Nishino E, Taniguchi T, Kameda T, Li Y, Saji F, Tanizawa O
Department of Obstetrics and Gynecology, Osaka University Medical School, Japan.
J Clin Endocrinol Metab. 1991 Mar;72(3):594-601. doi: 10.1210/jcem-72-3-594.
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 alpha, and its release was dependent on the rIL-1 alpha concentration used. The rIL-1 alpha-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 PM1, an anti-IL-6-R monoclonal antibody. Identical results were observed with rIL-1 beta. 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 PM1. 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.
白细胞介素-1（IL-1）具有独特的活性，可刺激多种人类和鼠类内分泌系统中多种激素的释放。IL-6也通过激活IL-6受体（R）介导的信号转导途径表现出此类活性。由于胎盘会产生这两种细胞因子以及诸如hCG等内分泌激素，我们研究了这些细胞因子如何调节正常滋养层细胞释放hCG。通过Percoll密度梯度纯化的滋养层细胞在受到重组（r）IL-1α刺激后120分钟开始释放hCG，其释放取决于所用的rIL-1α浓度。如通过IL-6依赖性细胞系MH60.BSF2细胞所测定，rIL-1α刺激的滋养层细胞先前释放了一种具有IL-6活性的分子。释放分子的IL-6特性通过山羊抗IL-6抗血清得以证实。用抗IL-6-R单克隆抗体PM1预处理滋养层细胞后，rIL-1介导的滋养层细胞hCG释放完全降至基础水平。用rIL-1β也观察到了相同的结果。这些结果表明，rIL-1诱导的hCG释放在人滋养层细胞中完全依赖于IL-6和IL-6-R介导的信号转导。然而，纯化的滋养层细胞组分中存在外周单核细胞，在它们最大程度释放后会导致IL-6和hCG释放迅速减少，这表明滋养层细胞与单核细胞之间存在某种调节相互作用。相比之下，与未刺激的滋养层细胞相比，在24小时时不再观察到rIL-1介导的纯化滋养层细胞IL-6和hCG分泌增强，而用PM1预处理滋养层细胞可显著抑制hCG的自发分泌。结果表明，除IL-1外，IL-6和hCG的分泌可能还受多种因子调节，并且hCG的分泌及其释放依赖于滋养层细胞中的IL-6和IL-6-R系统。
