{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T09:59:20Z","timestamp":1791194360528,"version":"4.1.0"},"reference-count":43,"publisher":"The Endocrine Society","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2007,7,1]]},"abstract":"<jats:p>Although viral infection is thought to be associated with subacute thyroiditis and probably with autoimmune thyroid disease, possible changes in thyroid function during the prodromal period of infection or subclinical infection remain largely unknown. Recently, it was shown that pathogen-associated molecular patterns 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 human TSH, 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. Thyrocytes expressed ligands for dsRNA (TLR 3, CD14, and retinoic-acid-inducible protein-1) comparable with the TSH receptor. DNA microarray and real-time PCR analyses revealed that dsRNA increased the expression of mRNA for TLR3, IFN-\u03b2, IFN-regulating factors, proinflammatory cytokines, and class I major histocompatibility complex (MHC), whereas genes associated with thyroid hormonogenesis (sodium\/iodide symporter, peroxidase, deiodinases) were suppressed. In accordance to these data, Poly(I:C) suppressed TSH-induced 125I uptake and hormone synthesis dose dependently, accompanied by a decrease in the ratio of 125I-T3\/125I-T4 released into the culture medium, whereas peptidoglycan, lipopolysaccharides, or unmethylated CpG DNA, ligands for TLR2, TLR4, and TLR9, respectively, had no significant effect. These inhibitory effects of Poly(I:C) were not blocked by a neutralizing antibody against TLR3 and an anti-IFN \u03b1\/\u03b2 receptor antibody. 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.<\/jats:p>","DOI":"10.1210\/en.2006-1638","type":"journal-article","created":{"date-parts":[[2007,3,30]],"date-time":"2007-03-30T00:54:07Z","timestamp":1175216047000},"page":"3226-3235","source":"Crossref","is-referenced-by-count":35,"title":["Suppression of Iodide Uptake and Thyroid Hormone Synthesis with Stimulation of the Type I Interferon System by Double-Stranded Ribonucleic Acid in Cultured Human Thyroid Follicles"],"prefix":"10.1210","volume":"148","author":[{"given":"Kazuko","family":"Yamazaki","sequence":"first","affiliation":[{"name":"Thyroid Disease Institute (K.Y., E.Y., T.Y.), Kanaji Hospital, Tokyo 114-0015, Japan"},{"name":"Department of Surgery (K.Y., T.O.)Tokyo Women\u2019s Medical University, Tokyo 162-8666, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Suzuki","sequence":"first","affiliation":[{"name":"Department of Bioregulation (Ko.S.), National Institute of Infectious Diseases, Tokyo 189-0002, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emiko","family":"Yamada","sequence":"first","affiliation":[{"name":"Thyroid Disease Institute (K.Y., E.Y., T.Y.), Kanaji Hospital, Tokyo 114-0015, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsu","family":"Yamada","sequence":"first","affiliation":[{"name":"Thyroid Disease Institute (K.Y., E.Y., T.Y.), Kanaji Hospital, Tokyo 114-0015, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumihiko","family":"Takeshita","sequence":"first","affiliation":[{"name":"Department of Molecular Biodefense Research (F.T.), Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Misako","family":"Matsumoto","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology (M.M.), Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoaki","family":"Mitsuhashi","sequence":"first","affiliation":[{"name":"Saitama Medical School (T.M.), Saitama 350-3469, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takao","family":"Obara","sequence":"first","affiliation":[{"name":"Department of Surgery (K.Y., T.O.)Tokyo Women\u2019s Medical University, Tokyo 162-8666, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazue","family":"Takano","sequence":"first","affiliation":[{"name":"Department of Medicine (K.T., Ka.S.), Institute of Clinical Endocrinology, Tokyo Women\u2019s Medical University, Tokyo 162-8666, 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Evidence for a dual mechanism of induction.","volume":"138","author":"Khoury","year":"1991","journal-title":"Am J Pathol"},{"key":"2020071613052218200_R38","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1210\/endo-122-2-563","article-title":"Virus-induced thyroiditis.","volume":"122","author":"Srinivasappa","year":"1988","journal-title":"Endocrinology"},{"key":"2020071613052218200_R39","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1089\/105072501300042703","article-title":"Amiodarone stimulates interleukin-6 production in cultured human thyrocytes, exerting cytotoxic effects on thyroid follicles in suspension culture.","volume":"11","author":"Nakajima","year":"2001","journal-title":"Thyroid"},{"key":"2020071613052218200_R40","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1210\/jcem-27-9-1275","article-title":"Circulating viral and thyroid antibodies in subacute thyroiditis.","volume":"27","author":"Volpe","year":"1967","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071613052218200_R41","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1126\/science.1094823","article-title":"How viruses enter animal cells.","volume":"304","author":"Smith","year":"2004","journal-title":"Science"},{"key":"2020071613052218200_R42","first-page":"577","article-title":"Silent thyroiditis and subacute thyroiditis","author":"Lazarus","year":"1996","journal-title":"In: Braverman LE, Utiger RD, eds. 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