A study on the interferon-γ activated intracellular signal transduction pathway in the thyroid

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【IRF-1 study】Interferon regulatory factor-1 (IRF-1), an interferon (IFN)-inducible transcription factor, is expressed in the thyroid and implicated in the regulation of thyroid function and in the pathogenesis of autoimmune thyroid disease (AITD). To examine the role of IRF-1 in the development of AITD, the frequency and severity of thyroiditis were assessed in nonobese diabetic (NOD) mice, an animal model of Hashimoto's thyroiditis, lacking IRF-1 gene. While more than 80 % of 14 week-old iodide ingested IRF-1 +/+ and +/- mice developed lymphocytic thyroiditis (LT), no -/- mice developed LT. In contrast, 24 week-old mice and thyroglobulin (Tg)immunized mice developed thyroiditis regardless of IRF-1. In the latter, no significant difference was found in the severity of thyroiditis. In IRF-1 -/- mice, CD8+T cells and IFN-γ secretion were decreased in the spleen. These results suggest that CD8+ T cells and Th1 reaction are involved in the development of iodide-induced LT in IRF-1 deficient NOD mice. However, different mechanism may be involved in spontaneous and Tg-induced thyroiditis in NOD mice.【PKR study】Double-stranded RNA (dsRNA) dependent protein kinase (PKR) play a role in the antiviral responses as well as the regulation of cell function. We demonstrated the presence of PKR in FRTL-5 rat thyroid cells. Addition of dsRNA to FRTL-5 cells resulted in phosphorylation of eukaryotic initiation factor-2 and iκBα and induction of NFκB binding. In addition, type I IFN, especially IFN-β, and IRF-1 gene expression and STAT-1 phosphorylation were induced in dsRNA-stimulated cells. These results suggest that dsRNA activated signal transduction pathway may play a role in the regulation of thyroid function and may be involved in the pathogenesis of AITD.