Thyroid-stimulating hormone induces interleukin-18 gene expression in FRTL-5 cells: immunohistochemical detection of interleukin-18 in autoimmune thyroid disease.

Copyright 2002 Mary Ann Liebert, Inc. publisherInterleukin(IL)‐l8 is a cloned cytokine that was identified originally as a factor having potent interferon(IFN)‐γ-inducing activity on Kupffer cells. First, we analyzed lL-18 gene expression by reverse transcription-polymerase chain reaction(RT-PCR) in rat thyroid FRTL-5 cells and human thyroid tissue samples. The expression of IL-18mRNA in FRTL-5 cells was enhanced by thryoid-stimulating hormone(TSH) in a dose-dependent manner. 8-Bromo-cyclic adenosine monophosphate(cAMP） also increased in lL-18 mRNA levels. Furthermore, TGCT clones that exhibited an increase in intracellular cAMP accumulation showed an increased IL-l8 mRNA signal when compared to controls. Taken together, these data suggested that the effect of TSH on IL-18 gene expression was mediated by activating protein kinase A. Treatment of FRTL-5 cells with the antithyroid drug, methimazole(MMI), suppressed this stimulatory action of TSH on IL-18 gene expression. Next, we examined IL-18 expression in human thyroid tissue derived from patients with autoimmune thyroid diseases(ATD). RTPCR and immunohistology demonstrated that human thyroid follicular cells expressed lL-18. Especially in thyroid tissue from a patient with Hashimoto's thyroiditis, expression was more diffuse and extensive, generally observed in close relation to a lymphocytic infiltrate. Also, IL-18 protein was distributed in the same follicles that express Fas-L and HLA-DR. This study is the first to demonstrate the detection of lL-l8 in the thyroid gland. The frequent expression of IL-l8 in thyrocytes suggests that IL-18 itself might be a secreted immunomodulator in ATD