Thyrocyte interleukin-18 expression is up-regulated by interferon-γ and may contribute to thyroid destruction in Hashimoto's thyroiditis - PubMed (original) (raw)

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

Zhe Liu et al. Int J Exp Pathol. 2010 Oct.

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.

© 2010 The Authors. Journal compilation © 2010 Blackwell Publishing Ltd.

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Figures

Figure 1

Figure 1

Up-regulation of IL-18 expression in the thyroid follicular cells (TFCs) of patients with Hashimoto's thyroiditis (HT). Histological sections were stained with haematoxylin-eosin in the thyroid tissues of control (a) and HT (b). RT-PCR analysis showed that constitutive IL-18 mRNA expression was observed in the control thyroid tissues and dramatically increased in the thyroid tissues of HT. n = 6. P < 0.05, vs. control (c). In immunohistochemical staining, IL-18-positive cells were barely detected in the control thyroid tissues (d). More diffuse and stronger staining for IL-18 was found in the thyroid tissues of HT, and the expression was mainly localized in the cytoplasm of TFCs (e). The staining omitted the step with anti-human IL-18 antibody in those of HT was included as negative control (f). Magnification 200×.

Figure 2

Figure 2

Effect of IFN-γ on IL-18 expression in isolated TFCs. Human TFCs were incubated for 48 h with different cytokines. RT-PCR analysis showed that IL-18 mRNA was constitutively expressed in control cells. The expression was up-regulated by 250 U/ml IFN-γ rather than 500 U/ml TNF-α or 50 U/ml IL-1β (a). IFN-γ dose-dependently stimulated IL-18 mRNA expression in the cells (b). Western blot analysis showed that a 24-kDa protein, consistent with rh-pro-IL-18 loaded in positive control lane, was found in the lysates of control cells. The expression was increased in the lysates of IFN-γ-treated cells. However, an 18-kDa mature IL-18 was undetected in the lysates from both groups of cells (c). Data were obtained from four independent experiments in a and two in b–c. *P < 0.05, vs. control.

Figure 3

Figure 3

Immunofluorescent staining of IL-18 and thyroglobulin in isolated human TFCs treated with IFN-γ. Green colour showed thyroglobulin expression (a). Red colour showed IL-18 expression (b). Yellow colour indicated co-expression of IL-18 and thyroglobulin (c). Magnification 200×.

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