دورية أكاديمية
Genomic control of inflammation in experimental atopic dermatitis
العنوان: | Genomic control of inflammation in experimental atopic dermatitis |
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المؤلفون: | Yan Liu, Jozef Zienkiewicz, Huan Qiao, Katherine N. Gibson-Corley, Kelli L. Boyd, Ruth Ann Veach, Jacek Hawiger |
المصدر: | Scientific Reports, Vol 12, Iss 1, Pp 1-11 (2022) |
بيانات النشر: | Nature Portfolio, 2022. |
سنة النشر: | 2022 |
المجموعة: | LCC:Medicine LCC:Science |
مصطلحات موضوعية: | Medicine, Science |
الوصف: | Abstract Atopic Dermatitis (AD) or eczema, a recurrent allergic inflammation of the skin, afflicts 10–20% of children and 5% adults of all racial and ethnic groups globally. We report a new topical treatment of AD by a Nuclear Transport Checkpoint Inhibitor (NTCI), which targets two nuclear transport shuttles, importin α5 and importin β1. In the preclinical model of AD, induced by the active vitamin D3 analog MC903 (calcipotriol), NTCI suppressed the expression of keratinocyte-derived cytokine, Thymic Stromal Lymphopoietin (TSLP), the key gene in AD development. Moreover, the genes encoding mediators of TH2 response, IL-4 and its receptor IL-4Rα were also silenced together with the genes encoding cytokines IL-1β, IL-6, IL-13, IL-23α, IL-33, IFN-γ, GM-CSF, VEGF A, the chemokines RANTES and IL-8, and intracellular signal transducers COX-2 and iNOS. Consequently, NTCI suppressed skin infiltration by inflammatory cells (eosinophils, macrophages, and CD4 + T lymphocytes), and reduced MC903-evoked proliferation of Ki-67-positive cells. Thus, we highlight the mechanism of action and the potential utility of topical NTCI for treatment of AD undergoing Phase 1/2 clinical trial (AMTX-100 CF, NCT04313400). |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 2045-2322 |
Relation: | https://doaj.org/toc/2045-2322 |
DOI: | 10.1038/s41598-022-23042-x |
URL الوصول: | https://doaj.org/article/6c7e591c508045cfb18112d5daf1ccda |
رقم الأكسشن: | edsdoj.6c7e591c508045cfb18112d5daf1ccda |
قاعدة البيانات: | Directory of Open Access Journals |
تدمد: | 20452322 |
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DOI: | 10.1038/s41598-022-23042-x |