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DITRA causes systemic autoinflammatory diseases, including generalized pustular psoriasis (GPP), an occasionally life-threatening disease that is characterized by widespread sterile pustules on the skin, fever and other systemic symptoms. GPP can present at any age, and provocative factors include various infections, medicines and pregnancy. Objective: We aimed to elucidate the role of toll-like receptor 4 (TLR4) signaling in DITRA and to innovate an efficient treatment for DITRA. Methods: We generated Il36rn\u2212/\u2212 mice and treated them with TLR4 agonist to establish DITRA model mice. Furthermore, we administrated TLR4 antagonist TAK-242 to the model mice to inhibit the DITRA symptoms. Result: Il36rn\u2212/\u2212 mice treated by TLR4 agonist showed autoinflammatory symptoms in skin, articulation and liver. Thus, we established model mice for DITRA or GPP that show cutaneous, articular, and hepatic autoinflammatory symptoms typical of DITRA or GPP: sterile pustules on the skin, liver abscesses and enthesitis of the hind paws. Additionally, these symptoms were canceled by TAK-242 administration. We demonstrated the inhibitory effects of the TLR4 antagonist TAK-242 on the autoinflammatory symptoms exhibited by the DITRA models. 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Toll-like receptor 4 antagonist TAK-242 inhibits autoinflammatory symptoms in DITRA
http://hdl.handle.net/2237/26851
7d686741-9564-4ae0-9d2e-9c974fe63189
名前 / ファイル | ライセンス | アクション | |
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2017-08-01 | |||||
タイトル | ||||||
タイトル | Toll-like receptor 4 antagonist TAK-242 inhibits autoinflammatory symptoms in DITRA | |||||
著者 |
Shibata, Akitaka
× Shibata, Akitaka× Sugiura, Kazumitsu× Furuta, Yasuhide× Mukumoto, Yoshiko× Kaminuma, Osamu× Akiyama, Masashi |
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権利 | ||||||
権利情報 | © 2017. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Autoinflammation | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Deficiency of IL-36 receptor antagonist | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Generalized pustular psoriasis | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Toll-like receptor 4 | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | LPS | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | TAK-242 | |||||
抄録 | ||||||
内容記述 | Background: IL36RN encodes the IL-36 receptor antagonist (IL-36Ra), and loss-of-function mutations in IL36RN define a recessively inherited autoinflammatory disease named “deficiency of IL-36Ra” (DITRA). DITRA causes systemic autoinflammatory diseases, including generalized pustular psoriasis (GPP), an occasionally life-threatening disease that is characterized by widespread sterile pustules on the skin, fever and other systemic symptoms. GPP can present at any age, and provocative factors include various infections, medicines and pregnancy. Objective: We aimed to elucidate the role of toll-like receptor 4 (TLR4) signaling in DITRA and to innovate an efficient treatment for DITRA. Methods: We generated Il36rn−/− mice and treated them with TLR4 agonist to establish DITRA model mice. Furthermore, we administrated TLR4 antagonist TAK-242 to the model mice to inhibit the DITRA symptoms. Result: Il36rn−/− mice treated by TLR4 agonist showed autoinflammatory symptoms in skin, articulation and liver. Thus, we established model mice for DITRA or GPP that show cutaneous, articular, and hepatic autoinflammatory symptoms typical of DITRA or GPP: sterile pustules on the skin, liver abscesses and enthesitis of the hind paws. Additionally, these symptoms were canceled by TAK-242 administration. We demonstrated the inhibitory effects of the TLR4 antagonist TAK-242 on the autoinflammatory symptoms exhibited by the DITRA models. Conclusion: We suggested that blockage of TLR4 signaling is a promising treatment for DITRA and GPP. | |||||
内容記述タイプ | Abstract | |||||
出版者 | ||||||
出版者 | Elsevier | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源タイプresource | http://purl.org/coar/resource_type/c_6501 | |||||
タイプ | journal article | |||||
ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 0896-8411 | |||||
書誌情報 |
Journal of Autoimmunity 巻 80, p. 28-38, 発行日 2017-06 |
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著者版フラグ | ||||||
値 | author | |||||
URI | ||||||
識別子 | https://doi.org/10.1016/j.jaut.2017.01.007 | |||||
識別子タイプ | DOI | |||||
URI | ||||||
識別子 | http://hdl.handle.net/2237/26851 | |||||
識別子タイプ | HDL |