WEKO3
アイテム
インターロイキン18の表皮性魚鱗癬における重症度マーカーおよび新規治療標的としての有用性の検討
http://hdl.handle.net/10191/0002001051
http://hdl.handle.net/10191/0002001051fe697be1-6477-433a-86b3-98b6576a08e5
名前 / ファイル | ライセンス | アクション |
---|---|---|
本文 (1.18MB)
|
|
|
要旨 (527KB)
|
|
Item type | 学位論文 / Thesis or Dissertation(1) | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
公開日 | 2023-07-26 | |||||||||
タイトル | ||||||||||
タイトル | Interleukin-18 as a severity marker and novel potential therapeutic target for epidermolytic ichthyosis | |||||||||
言語 | en | |||||||||
タイトル | ||||||||||
タイトル | インターロイキン18の表皮性魚鱗癬における重症度マーカーおよび新規治療標的としての有用性の検討 | |||||||||
言語 | ja | |||||||||
言語 | ||||||||||
言語 | eng | |||||||||
資源タイプ | ||||||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||||||
資源タイプ | doctoral thesis | |||||||||
アクセス権 | ||||||||||
アクセス権 | open access | |||||||||
アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||||||
著者 |
安齋, 理
× 安齋, 理
|
|||||||||
抄録 | ||||||||||
内容記述タイプ | Abstract | |||||||||
内容記述 | Background Epidermolytic ichthyosis (EI) is a major form of nonsyndromic inherited ichthyosis, characterized by erythroderma, marked hyperkeratosis and scale, bulla and erosion at birth, associated with KRT1/KRT10 mutations. The cytokine and chemokine profiles in EI are poorly understood, and specific treatment options have not been established. Aim To explore novel biomarkers and therapeutic targets in patients with EI. Methods We analysed cytokine levels in serum and skin samples from 10 patients with inherited ichthyosis, including seven patients with EI. Wild-type and mutant KRT1 constructs were established and transfected into HaCaT cells, an immortalized keratinocyte cell line, for in vitro immunoblotting and immunocytochemistry analyses. Results Multiplex cytokine/chemokine analysis revealed that 10 cytokines/chemokines [interleukin (IL)-1β, IL-4, IL-17A, IL-16, IL-18, IL-1 receptor-α, macrophage colony-stimulating factor, interferon-α2, basic fibroblast growth factor and monocyte chemotactic protein-3] were significantly increased in patients with EI. Furthermore, IL-18 levels were significantly higher in patients with EI [n=7; 2714.1(1438.0) pg mL-1] than in healthy controls [n=11; 218.4(28.4) pg mL-1, P<0.01]. Immunohistochemical analyses showed that IL-18 expression was elevated in skin samples from patients with EI. Serum IL-18 levels correlated with the severity of ichthyosis, as measured by the Ichthyosis Scoring System. Immunoblotting analysis revealed that mature IL-18 levels were increased in the supernatant of mutant KRT1 expressing HaCaT cells. Additionally, these cells showed NLRP3 aggregation in the cytoplasm and ASC clustered around mutant keratin aggregations. These findings suggest that mutant keratin might promote the activation of the NLRP3 inflammasome and its downstream caspase-1-mediated IL-18 release in keratinocytes from patients with EI. Conclusions Our results suggest that serum IL-18 is a severity marker released from the skin of patients with EI. Blockade of IL-18 may be a useful novel therapeutic option for patients with EI. | |||||||||
言語 | en | |||||||||
内容記述 | ||||||||||
内容記述タイプ | Other | |||||||||
内容記述 | Clinical and Experimental Dermatology. 2023, 48(3), 199–210. | |||||||||
言語 | en | |||||||||
DOI | ||||||||||
識別子タイプ | DOI | |||||||||
関連識別子 | https://doi.org/10.1093/ced/llac069 | |||||||||
権利 | ||||||||||
言語 | en | |||||||||
権利情報 | © The Author(s) 2022. | |||||||||
学位名 | ||||||||||
言語 | ja | |||||||||
学位名 | 博士(医学) | |||||||||
学位授与機関 | ||||||||||
学位授与機関識別子Scheme | kakenhi | |||||||||
学位授与機関識別子 | 13101 | |||||||||
言語 | ja | |||||||||
学位授与機関名 | 新潟大学 | |||||||||
言語 | en | |||||||||
学位授与機関名 | Niigata University | |||||||||
学位授与年月日 | ||||||||||
学位授与年月日 | 2023-03-23 | |||||||||
学位授与番号 | ||||||||||
学位授与番号 | 甲第5113号 | |||||||||
学位記番号 | ||||||||||
内容記述タイプ | Other | |||||||||
内容記述 | 新大院博(医)第1104号 | |||||||||
言語 | ja |