Thyrocytes contribute to their own demise: the role of interleukin-18 in Hashimoto's thyroiditis

Abstract

To investigate the IL-18 expression in the thyroid tissues of Hashimoto's thyroiditis (HT) and its cellular localization and the effect of interferon-gamma (IFN-gamma) on the interleukin- (IL)-18 expression in thyrocytes. RT-PCR and immunohistochemistry were used to detect the IL-18 expression and its cellular localization in the thyroid tissues biopsy specimens of 6 HT patients with normal thyroid function, 6 normal thyroid specimens resected from patients with pharyngeal carcinoma, and 16 specimens of thyroid tissues adjacent to the thyroid adenoma obtained during operation. Thyrocytes were isolated, cultured, and exposed to IL-1beta, tumor necrosis factor-alpha (TNF-alpha), or IFN-gamma for 48 h. RT-PCR and Western blotting were used to detect the IL-18 expression. IL-18 mRNA expression was at an extremely low levels in the normal thyroid tissues and at a significantly higher level in the thyroid tissues of HT. Immunohistochemical staining showed that IL-18 expression was augmented in the thyroid tissues of HT and was mainly localized in the thyroid follicular cells. The IL-18 mRNA expression in the isolated human thyrocytes was dose-dependently elevated by IFN-gamma rather than TNF-alpha or IL-1beta. Western blotting showed that pro-IL-18, but not mature IL-18, was detected in the lysates of the cultured human thyrocytes and the expression of pro-IL-18 was increased by IFN-gamma. IL-18 expression is elevated in the thyroid follicular cells of HT. IL-18 is constitutively expressed in the isolated human thyrocytes and its expression is up-regulated by IFN-gamma. Therefore, interplay between IL-18 and IFN-gamma may have an important role in the thyrocytes destruction in HT.