Kawabe Y, Eguchi K, Shimomura C, Mine M, Otsubo T, Ueki Y, Tezuka H, Nakao H, Kawakami A, Migita K
First Department of Internal Medicine, Nagasaki University School of Medicine, Japan.
J Clin Endocrinol Metab. 1989 Jun;68(6):1174-83. doi: 10.1210/jcem-68-6-1174.
This study was undertaken to determine the effects of interleukin-1 (IL-1) on human thyroid epithelial cells (thyrocytes) and whether thyrocytes produce IL-1. The supernatants of cultured peripheral blood monocytes stimulated with lipopolysaccharide (LPS) increased [3H]thymidine incorporation into thyrocytes from normal subjects and patients with Grave's disease. The IL-1 levels of cultured supernatants of monocytes were measured by a thymocyte costimulation assay and a solid phase sandwich immunoenzymometric assay. The supernatants of monocyte cultures stimulated with LPS contained significant amounts of IL-1 bioactivity and IL-1 alpha and IL-1 beta immunoactivity. Recombinant IL-1 beta (rIL-1 beta) also stimulated [3H]thymidine incorporation into thyrocytes from normal subjects and patients with Graves' disease, and it increased the proportion of thyrocytes in the S phase of the cell cycle. Furthermore, thyrocytes stimulated with rIL-1 beta for 24 h produced significant amounts of prostaglandin E2. Indomethacin inhibited completely the rIL-1 beta-stimulated prostaglandin E2 production and increased markedly [3H]thymidine incorporation. IL-1-like activity also was detected in the cultured supernatants of lipopolysaccharide (LPS)-stimulated thyrocytes from Graves' and normal thyroid glands, but the amount of IL-1-like activity secreted by thyrocytes was significantly less than that secreted by circulating monocytes. The kinetics of the release of IL-1-like activity by thyrocytes were similar to those of its production by circulating monocytes. Pretreatment of thyrocytes with interferon-gamma failed to enhance the release of IL-1-like activity. Moreover, IL-1 alpha or IL-1 beta immunoreactivity could not be detected in the supernatants of LPS-stimulated thyrocytes, despite the presence of IL-1-like bioactivity. No IL-1 alpha mRNA was detected in unstimulated thyrocytes or thyrocytes stimulated with LPS and phorbol myristate acid. These findings demonstrate that thyrocytes produce an IL-1-like substance(s), but not IL-1, when stimulated by LPS. We conclude that IL-1 may regulate the proliferation of thyrocytes and that local production of IL-1 by infiltrating monocytes may contribute to the development of goiter in patients with autoimmune thyroid diseases.
本研究旨在确定白细胞介素-1（IL-1）对人甲状腺上皮细胞（甲状腺细胞）的影响以及甲状腺细胞是否产生IL-1。用脂多糖（LPS）刺激培养的外周血单核细胞的上清液可增加正常受试者和格雷夫斯病患者甲状腺细胞中[3H]胸腺嘧啶核苷的掺入。单核细胞培养上清液中的IL-1水平通过胸腺细胞共刺激试验和固相夹心免疫酶测定法进行测量。用LPS刺激的单核细胞培养上清液含有大量的IL-1生物活性以及IL-1α和IL-1β免疫活性。重组IL-1β（rIL-1β）也刺激正常受试者和格雷夫斯病患者的甲状腺细胞掺入[3H]胸腺嘧啶核苷，并增加细胞周期S期甲状腺细胞的比例。此外，用rIL-1β刺激24小时的甲状腺细胞产生大量前列腺素E2。吲哚美辛完全抑制rIL-1β刺激的前列腺素E2产生，并显著增加[3H]胸腺嘧啶核苷的掺入。在来自格雷夫斯病和正常甲状腺的LPS刺激的甲状腺细胞培养上清液中也检测到IL-1样活性，但甲状腺细胞分泌的IL-1样活性量明显少于循环单核细胞分泌的量。甲状腺细胞释放IL-1样活性的动力学与其由循环单核细胞产生的动力学相似。用干扰素-γ预处理甲状腺细胞未能增强IL-1样活性的释放。此外，尽管存在IL-1样生物活性，但在LPS刺激的甲状腺细胞上清液中未检测到IL-1α或IL-1β免疫反应性。在未刺激的甲状腺细胞或用LPS和佛波醇肉豆蔻酸刺激的甲状腺细胞中未检测到IL-1α mRNA。这些发现表明，LPS刺激时甲状腺细胞产生一种IL-1样物质，但不产生IL-1。我们得出结论，IL-1可能调节甲状腺细胞的增殖，并且浸润单核细胞局部产生IL-1可能有助于自身免疫性甲状腺疾病患者甲状腺肿的发展。
