Abstract
Interferon-γ (IFN-γ) has a direct role in thyroid destruction in autoimmune thyroiditis. Interleukin-18 (IL-18), a pro-inflammatory cytokine with potent IFN-γ inducing activities, may play an important role in Th1-mediated autoimmune diseases. The purpose of this study was to characterize the expression and localization of IL-18 in the thyroid tissues of Hashimoto's thyroiditis (HT) and to investigate the effect of IFN-γ on IL-18 expression in isolated human thyroid follicular cells (TFCs). Thyroid tissues obtained from six euthyroid patients with HT and six control subjects were used to detect IL-18 expression by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemical staining. Human TFCs were isolated and incubated for 48 h with or without IFN-γ, tumour necrosis factor-α (TNF-α) or IL-1β. IL-18 expression was analysed by RT-PCR, immunofluorescent double staining and western blot. We found that IL-18 expression was increased in the thyroid tissues of HT compared with control thyroid tissues. TFCs were major cell types expressing IL-18 in the thyroid tissues of HT. IL-18 was constitutively expressed in isolated human TFCs, and the expression was significantly up-regulated by IFN-γ rather than TNF-α or IL-1β. Western bolt revealed that a 24-kDa band corresponding to pro-IL-18 was broadened in the lysates of IFN-γ-treated TFCs. Our results demonstrated that IL-18 expression is up-regulated in the TFCs of HT patients and in primary human TFCs exposed to IFN-γ. Therefore, intrathyroidal interaction between IL-18 and IFN-γ may have a role in promoting the local immune response, which contributes to the thyroid destruction seen in HT.