Thyrocyte interleukin-18 expression is up-regulated by interferon-gamma and may contribute to thyroid destruction in Hashimoto's thyroiditis

P>Interferon-gamma (IFN-gamma) has a direct role in thyroid destruction in autoimmune thyroiditis. Interleukin-18 (IL-18), a pro-inflammatory cytokine with potent IFN-gamma 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-gamma 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-gamma, tumour necrosis factor-alpha (TNF-alpha) or IL-1 beta. 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-gamma rather than TNF-alpha or IL-1 beta. Western bolt revealed that a 24-kDa band corresponding to pro-IL-18 was broadened in the lysates of IFN-gamma-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-gamma. Therefore, intrathyroidal interaction between IL-18 and IFN-gamma may have a role in promoting the local immune response, which contributes to the thyroid destruction seen in HT.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000284319900004&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701PathologySCI(E)PubMed12ARTICLE5420-4259