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
| Autor: | Kazue Takano, Takao Obara, Emiko Yamada, Tomoaki Mitsuhashi, Misako Matsumoto, Kanji Sato, Koichi Suzuki, Fumihiko Takeshita, Tetsu Yamada, Kazuko Yamazaki |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Thyroid Hormones
endocrine system medicine.medical_specialty endocrine system diseases Thyroid Gland Gene Expression Thyrotropin Thyroid hormone receptor beta Endocrinology Thyroid peroxidase Internal medicine medicine Humans Cells Cultured Oligonucleotide Array Sequence Analysis RNA Double-Stranded Thyroid hormone receptor Dose-Response Relationship Drug biology Reverse Transcriptase Polymerase Chain Reaction Thyroid Antibodies Monoclonal Interferon-alpha Biological Transport Interferon-beta Iodides Immunohistochemistry Toll-Like Receptor 2 Toll-Like Receptor 3 Toll-Like Receptor 4 medicine.anatomical_structure Toll-Like Receptor 9 Interferon Type I TLR3 biology.protein Chromatography Thin Layer Thyroid function Interferon type I Signal Transduction medicine.drug Endocrine gland |
| Zdroj: | Endocrinology. 148:3226-3235 |
| ISSN: | 1945-7170 0013-7227 |
| DOI: | 10.1210/en.2006-1638 |
| Popis: | 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-β, 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 α/β 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. |
| Databáze: | OpenAIRE |
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