title: Thyrocyte interleukin-18 expression is up-regulated by interferon-γ and may contribute to thyroid destruction in Hashimoto's thyroiditis.
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.
authors.affiliation: Department of Endocrinology and Metabolism, Peking University Third Hospital, Beijing, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Liu
authors.forename: Haining
authors.initials: H
authors.lastname: Wang
authors.forename: Wenhua
authors.initials: W
authors.lastname: Xiao
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Liu
authors.forename: Tianpei
authors.initials: T
authors.lastname: Hong
mesh_terms: D000328:Adult; D001706:Biopsy; D002478:Cells, Cultured; D005260:Female; D015870:Gene Expression / Q000276:immunology; D050031:Hashimoto Disease / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D020382:Interleukin-18 / Q000235:genetics* / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D013961:Thyroid Gland / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation / Q000276:immunology
chemical_list: D020382:Interleukin-18; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma