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Endocrinological and Immunological Roles of Toll-like Receptor 3 in Culture Human Thyroid Follicles

Research Project

Project/Area Number 17590967
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Endocrinology
Research InstitutionTokyo Women's Medical University

Principal Investigator

SATO Kanji  Tokyo Women's Medical University, Graduate School of Medicine, Professor, 医学研究科, 教授 (60138857)

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)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
KeywordsToll-like receptor-3 / double-stranded RNA / type I interferon / thyroid follicles / subacute thyroiditis / vascular endothelial growth factor / thyroidal blood flow / inorganic iodide / Interferon-α / interferon-β / DNA microarray
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 … More 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

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (12 results)

All 2007 2006

All Journal Article (10 results) Book (2 results)

  • [Journal Article] Suppression of iodide uptake and thyroid hormone synthesis with stimulation of type I interferon system by double-stranded RNA (dsRNA) in cultured human thyroid follicles2007

    • Author(s)
      Yamazaki K, Suzuki K, Yamada E, Yamada T, Takeshita F, Matsumoto M, Mitsuhashi T, Obara T, Takano K, Sato K
    • Journal Title

      Endocrinology 148(In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Povidone iodine-induced overt hypothyroidism in a patient with prolonged habitual gargling : Urinary excretion of iodide after garaling in normal subjects.2007

    • Author(s)
      Sato K, Ohashi T, Ohmori T, Shiratori K, Kimura H, Takano K
    • Journal Title

      Intern Med 46(in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [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
    • 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)

    • Related Report
      2006 Final Research Report Summary
  • [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
    • 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)

    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Suppression of iodide uptake and thyroid hormone synthesis with stimulation of type I interferon system by double-stranded RNA (dsRNA) in cultured human thyroid follicles2007

    • Author(s)
      Yamazaki K, Suzuki K, Emiko Yamada E, Yamada T, Takeshita F, Matsumoto M, Mitsuhashi T, Obara T, Takano K, Sato K
    • Journal Title

      Endocrinology 148 (In revision)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 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 factors2006

    • Author(s)
      Yamada E, Yamazaki K, Takano K, Obara T, Sato K
    • Journal Title

      Thyroid 16

      Pages: 545-554

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Mild and short recurrence of type II amiodarone-induced thyrotoxicosis in three patients receiving amiodarone continuously for more than 10 years2006

    • Author(s)
      Sato K, Shiga T, Matsuda N, Onoda N, Takano K, Hagiwara N, Kasanuki H
    • Journal Title

      Endocr J 53

      Pages: 531-538

    • NAID

      10019269869

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [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
    • 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

    • Related Report
      2006 Final Research Report Summary
  • [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
    • 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

    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] DNA microarray analysis of effects of TSH, iodide, cytokines and therapeutic agents on gene expression in cultured human thyroid follicles2006

    • Author(s)
      Sato K, Yamazaki K, Yamada E, et al.
    • Journal Title

      DNA Microarra Analysis of Endocrine Cells in Health and Disease (edited by Handwerger S, Aronow B)(Humana Press) (in press)

    • Related Report
      2005 Annual Research Report
  • [Book] DNA Microarray Analysis of Endocrine Cells in Health and Disease ((edited by) Handwerger S & Aronow B)2007

    • Author(s)
      Sato K, Yamazaki K, Yamada E
    • Publisher
      DNA microarray analysis of effects of TSH, iodide, cytokines and therapeutic agents on gene expression in cultured human thyroid follicles (In press)
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Book] DNA Microarray Analysis of Endocrine Cells in Health and Disease (edited by) Handwerger S & Aronow B2007

    • Author(s)
      Sato K, Yamazaki K, Yamada E
    • Publisher
      DNA microarray analysis of effects of TSH, iodide, cytokines and therapeutic agents on gene expression in cultured himan thyroid follicles(in press)
    • Related Report
      2006 Annual Research Report

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Published: 2005-04-01   Modified: 2016-04-21  

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