2006 Fiscal Year Final Research Report Summary
Endocrinological and Immunological Roles of Toll-like Receptor 3 in Culture Human Thyroid Follicles
| Project/Area Number |
17590967
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Endocrinology
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| Research Institution | Tokyo Women's Medical University |
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Principal Investigator |
SATO Kanji Tokyo Women's Medical University, Graduate School of Medicine, Professor, 医学研究科, 教授 (60138857)
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| Co-Investigator(Kenkyū-buntansha) |
OBARA Takao Tokyo Women's Medical University, Professor, 医学部, 教授 (70090488)
SUZUKI Koichi National Institute of Infectious Diseases, Laboratory of Immunology, Chief, 病原部生物部, 室長 (20206478)
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| Project Period (FY) |
2005 – 2006
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| Keywords | Toll-like receptor-3 / double-stranded RNA / type I interferon / thyroid follicles / subacute thyroiditis / vascular endothelial growth factor / thyroidal blood flow / inorganic iodide |
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| Research Abstract |
Recently, it was shown that pathogen-associated molecular patterns (PAMPS) stimulate Toll-like receptors (TLR) and activate innate immune responses by producing type I interferons (IFN). Using a human thyroid follicle culture system, in which de novo synthesized thyroid hormones are released into the culture medium under physiological concentrations of hTSH, we studied the effects of polyinosinic-polycytidylic acid (Poly(I : C)), a chemical analog of viral double-stranded RNA (dsRNA), on TSH-induced thyroid function.
We found that thyrocytes expressed ligands for dsRNA (TLR3, CD14, and RIG-1) comparable to the TSH receptor. DNA microarray and real-time PCR analyses revealed that dsRNA increased the expression of mRNA for TLR3,IFN-β, interferon-regulating factors, proinflammatory cytokines, and class I MHC, whereas genes associated with thyroid hormonogenesis (NIS, peroxidase, deiodinases) were suppressed. In accordance to these data, Poly(I : C) suppressed TSH-induced ^<125>I uptake and
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hormone synthesis dose-dependently, accompanied by a decrease in the ratio of ^<125>I-T3/^<125>I-T4 released into the culture medium. These in vitro findings suggest that when thyrocytes are infected with certain viruses, dsRNA formed intracellularly in thyrocytes may be a cause for thyroid dysfunction, leading to development of autoimmune thyroiditis (Reference 3).
It is well known that inorganic iodide, when administered to hyperthyroid patients such as Graves' disease, decreases a thyroidal blood flow. To elucidate this mechanism, we studied the effects of inorganic iodide on vascular endothelial growth factor families in cultured human thyroid follicles in which Wolff-Chaikoff effect was well preserved. Using oligo-microarray which can analyze whole human genes (up to 41,000 gene spots), we found that iodide at high concentration decreased mRNA expression level of VEGF-A, VEGF-B and Placental growth factors, and increased urokinase-type plasminogen activator that produces angiostatin from plasmin.
These data suggest that iodide reduces a thyroidal blood flow by inhibiting the production of angiogenesis factors and stimulating the production of angiogenesis inhibitors (Reference 1). Less
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[Journal Article] 「研究成果報告書概要(欧文)」より2007
Author(s)
Yamazaki K, Suzuki K, Emiko Yamada E, Yamada T, Takeshita F, Matsumoto M
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Journal Title
Suppression of iodide uptake and thyroid hormone synthesis with stimulation of type I interferon system by double-stranded RNA (dsRNA) in cultured human thyroid follicles. (MitsuhashiT, Obara T, Takano K, Sato K) Endocrinology 148 (in press)
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[Journal Article] 「研究成果報告書概要(欧文)」より2007
Author(s)
Sato K, Ohashi T, Ohmori T, Shiratori K, Kimura H, Takano K
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Journal Title
Povidone iodine-induced overt hypothyroidism in a patient with prolonged habitual gargling : Urinary excretion of iodide after gargling in normal subjects Intern Med 46 (in press)
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[Journal Article] 「研究成果報告書概要(欧文)」より2006
Author(s)
Yamada E, Yamazaki K, Takano K, Obara T, Sato K
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Journal Title
Iodide inhibits vascular endothelial growth factor (VEGF)-A expression in cultured human thyroid follicles : a microarray search for effects of TSH and iodide on angiogenesis factors. Thyroid 16
Pages: 545-554
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[Journal Article] 「研究成果報告書概要(欧文)」より2006
Author(s)
Sato K, Shiga T, Matsuda N, Onoda N, Takano K, Hagiwara N, Kasanuki H
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Journal Title
Mild and short recurrence of type II amiodarone-induced thyrotoxicosis in three patients receiving amiodarone continuously for more than 10 years. Endocr J 53
Pages: 531-538
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