Therapeutic effect of selective interleukin-2-inducible tyrosine kinase inhibitor in orbital fibroblasts from patients with Graves’ orbitopathy
Interleukin-2-inducible tyrosine kinase (ITK) is a crucial cytoplasmic protein in the T-cell signaling pathway. Here, we aimed to demonstrate the anti-inflammatory effect of the selective IL-2-induced tyrosine kinase inhibitor BMS-509744 (BMS) on Graves’ orbitopathy (GO) in an in vitro model. ITK mR...
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The Japan Endocrine Society
2024-09-01
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| Series: | Endocrine Journal |
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| Online Access: | https://www.jstage.jst.go.jp/article/endocrj/71/9/71_EJ23-0729/_html/-char/en |
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| author | Yeonjung Yoon Hyun Young Park Min Kyung Chae Sun Young Jang Jin Sook Yoon |
| author_facet | Yeonjung Yoon Hyun Young Park Min Kyung Chae Sun Young Jang Jin Sook Yoon |
| author_sort | Yeonjung Yoon |
| collection | DOAJ |
| description | Interleukin-2-inducible tyrosine kinase (ITK) is a crucial cytoplasmic protein in the T-cell signaling pathway. Here, we aimed to demonstrate the anti-inflammatory effect of the selective IL-2-induced tyrosine kinase inhibitor BMS-509744 (BMS) on Graves’ orbitopathy (GO) in an in vitro model. ITK mRNA expression in orbital tissues from GO and normal controls was compared using real-time polymerase chain reaction (RT-PCR) and immunohistochemistry. Primary cultured orbital fibroblasts from each group were pretreated with BMS and stimulated with interleukin (IL)-1β to induce inflammatory reaction. ITK mRNA expression was evaluated using western blotting, and inflammatory cytokine production and downstream transcription factor expression were analyzed after pretreatment with BMS. ITK mRNA expression in GO tissues was significantly higher than that in normal control tissues. After stimulation with IL-1β, ITK phosphorylation significantly increased in both GO orbital and normal control tissues. BMS inhibited IL-1β-induced IL-8 expression in the GO orbital fibroblasts. BMS pretreatment significantly suppressed NF-κB phosphorylation in both GO and normal controls. The selective ITK inhibitor attenuates proinflammatory cytokine production and proinflammatory transcription factor phosphorylation in in vitro model of GO. |
| format | Article |
| id | doaj-art-80faa5db925a424196a053b7296ac10c |
| institution | Kabale University |
| issn | 1348-4540 |
| language | English |
| publishDate | 2024-09-01 |
| publisher | The Japan Endocrine Society |
| record_format | Article |
| series | Endocrine Journal |
| spelling | doaj-art-80faa5db925a424196a053b7296ac10c2025-01-22T05:20:11ZengThe Japan Endocrine SocietyEndocrine Journal1348-45402024-09-0171985186110.1507/endocrj.EJ23-0729endocrjTherapeutic effect of selective interleukin-2-inducible tyrosine kinase inhibitor in orbital fibroblasts from patients with Graves’ orbitopathyYeonjung Yoon0Hyun Young Park1Min Kyung Chae2Sun Young Jang3Jin Sook Yoon4The Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul 03722, Republic of KoreaThe Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul 03722, Republic of KoreaThe Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul 03722, Republic of KoreaDepartment of Ophthalmology, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon 14584, KoreaThe Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul 03722, Republic of KoreaInterleukin-2-inducible tyrosine kinase (ITK) is a crucial cytoplasmic protein in the T-cell signaling pathway. Here, we aimed to demonstrate the anti-inflammatory effect of the selective IL-2-induced tyrosine kinase inhibitor BMS-509744 (BMS) on Graves’ orbitopathy (GO) in an in vitro model. ITK mRNA expression in orbital tissues from GO and normal controls was compared using real-time polymerase chain reaction (RT-PCR) and immunohistochemistry. Primary cultured orbital fibroblasts from each group were pretreated with BMS and stimulated with interleukin (IL)-1β to induce inflammatory reaction. ITK mRNA expression was evaluated using western blotting, and inflammatory cytokine production and downstream transcription factor expression were analyzed after pretreatment with BMS. ITK mRNA expression in GO tissues was significantly higher than that in normal control tissues. After stimulation with IL-1β, ITK phosphorylation significantly increased in both GO orbital and normal control tissues. BMS inhibited IL-1β-induced IL-8 expression in the GO orbital fibroblasts. BMS pretreatment significantly suppressed NF-κB phosphorylation in both GO and normal controls. The selective ITK inhibitor attenuates proinflammatory cytokine production and proinflammatory transcription factor phosphorylation in in vitro model of GO.https://www.jstage.jst.go.jp/article/endocrj/71/9/71_EJ23-0729/_html/-char/engraves’ orbitopathyinflammationinterleukin-2 inducible tyrosine kinaseorbital fibroblastthyroid eye disease |
| spellingShingle | Yeonjung Yoon Hyun Young Park Min Kyung Chae Sun Young Jang Jin Sook Yoon Therapeutic effect of selective interleukin-2-inducible tyrosine kinase inhibitor in orbital fibroblasts from patients with Graves’ orbitopathy Endocrine Journal graves’ orbitopathy inflammation interleukin-2 inducible tyrosine kinase orbital fibroblast thyroid eye disease |
| title | Therapeutic effect of selective interleukin-2-inducible tyrosine kinase inhibitor in orbital fibroblasts from patients with Graves’ orbitopathy |
| title_full | Therapeutic effect of selective interleukin-2-inducible tyrosine kinase inhibitor in orbital fibroblasts from patients with Graves’ orbitopathy |
| title_fullStr | Therapeutic effect of selective interleukin-2-inducible tyrosine kinase inhibitor in orbital fibroblasts from patients with Graves’ orbitopathy |
| title_full_unstemmed | Therapeutic effect of selective interleukin-2-inducible tyrosine kinase inhibitor in orbital fibroblasts from patients with Graves’ orbitopathy |
| title_short | Therapeutic effect of selective interleukin-2-inducible tyrosine kinase inhibitor in orbital fibroblasts from patients with Graves’ orbitopathy |
| title_sort | therapeutic effect of selective interleukin 2 inducible tyrosine kinase inhibitor in orbital fibroblasts from patients with graves orbitopathy |
| topic | graves’ orbitopathy inflammation interleukin-2 inducible tyrosine kinase orbital fibroblast thyroid eye disease |
| url | https://www.jstage.jst.go.jp/article/endocrj/71/9/71_EJ23-0729/_html/-char/en |
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