Thyroid-stimulating hormone induces interleukin-18 gene expression in FRTL-5 cells: immunohistochemical detection of interleukin-18 in autoimmune thyroid disease.
Interleukin (IL)-18 is a cloned cytokine that was identified originally as a factor having potent interferon (IFN)-gamma-inducing activity on Kupffer cells. First, we analyzed IL-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-18 mRNA 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 IL-18 mRNA levels. Furthermore, TGCT clones that exhibited an increase in intracellular cAMP accumulation showed an increased IL-18 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). RT-PCR and immunohistology demonstrated that human thyroid follicular cells expressed IL-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 IL-18 in the thyroid gland. The frequent expression of IL-18 in thyrocytes suggests that IL-18 itself might be a secreted immunomodulator in ATD.
Takiyama
Yumi
Y
Second Department of Pathology, Asahikawa Medical College, Asahikawa, Tokyo, Japan. taka0716@asahikawa-med.ac.jp
Miyokawa
Naoyuki
N
Tokusashi
Yoshihiko
Y
Ito
Koichi
K
Kato
Shizuo
S
Kimura
Shoji
S
Sato
Keisuke
K
Katagiri
Makoto
M
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D013956:Antithyroid Agents / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D007150:Immunohistochemistry; D020382:Interleukin-18 / Q000032:analysis / Q000235:genetics*; D007476:Ionophores / Q000494:pharmacology; D008713:Methimazole / Q000494:pharmacology; D016612:Paraffin Embedding; D010960:Plasminogen Activators / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013961:Thyroid Gland / Q000737:chemistry / Q000166:cytology / Q000502:physiology*; D013967:Thyroiditis, Autoimmune / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D013972:Thyrotropin / Q000494:pharmacology*; D010959:Tissue Plasminogen Activator / Q000494:pharmacology
D013956:Antithyroid Agents; D020382:Interleukin-18; D007476:Ionophores; D012333:RNA, Messenger; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000001:Calcimycin; D008713:Methimazole; D013972:Thyrotropin; D011493:Protein Kinase C; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator; D002118:Calcium