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Phellopterin alleviates atopic dermatitis-like inflammation and suppresses IL-4-induced STAT3 activation in keratinocytes

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机构： [1]Engineering Research Center of Sichuan-Tibet Traditional Medicinal Plant, Chengdu University, Chengdu 610106, China [2]Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, NO. 110, Ganhe Road, Shanghai 200437, China [3]Institute of Cancer Biology and Drug Discovery, Chengdu University, Chengdu 610106, China [4]School of Basic Medical Sciences, Chengdu University, NO. 2025, Chengluo Road, Chengdu 610106, China [5]Key Laboratory of Clinical Genetics, Affiliated Hospital of Chengdu University, Chengdu 610106, China [6]School of Food and Biological Engineering, Chengdu University, Chengdu 610106, China [7]School of Pharmacy, Chengdu University, Chengdu 610106, China

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关键词： Atopic dermatitis Phellopterin STAT3 activation TSLP IL-33

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Anti-inflammation medication is one of the most important treatment for people with atopic dermatitis (AD) which presents persistent type 2 inflammation in skin lesions. Interaction between activated keratinocytes and immune cells in AD skin lesions amplifies inflammatory signaling by augmenting production of cytokines, such as keratinocyte-derived thymic stromal lymphopoietin (TSLP) and interleukin-33 (IL-33). Phellopterin is a bioactive compound isolated from ethanol extract of Angelica dahurica root which has been traditionally used for AD therapy in China. In the present study, we showed that Phellopterin possessed anti-type 2 inflammation activity and alleviated AD-like phenotypes including reduction in serum immunoglobulin E (IgE) levels and infiltration of eosinophils and mast cells in the AD-like skin lesions. Further molecular analysis found that Phellopterin suppressed phosphorylation of signal transducer and activator of transcription 3 (STAT3) at Tyr705, and the expression of TSLP and IL-33 in epidermal keratinocytes of AD-like lesions. In vitro studies in cultured human keratinocytes demonstrated that STAT3 was required for interleukin-4 (IL-4)-induced overexpression of TSLP and IL-33. Phellopterin inhibited IL-4-induced activation of STAT3, which leaded to suppress the STAT3-mediated transcription of TSLP and IL-33. Our study suggested that Phellopterin is an active compound with bioactivities of anti- type 2 inflammation and STAT3 inactivation, thus allowing to be a promising candidate for AD topical therapy.Copyright © 2022 Elsevier B.V. All rights reserved.

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出版当年[2022]版：

大类 | 2 区医学

小类 | 2 区免疫学 2 区药学

最新[2023]版：

大类 | 2 区

医学

小类 | 2 区免疫学 2 区药学

第一作者：

第一作者机构： [1]Engineering Research Center of Sichuan-Tibet Traditional Medicinal Plant, Chengdu University, Chengdu 610106, China [3]Institute of Cancer Biology and Drug Discovery, Chengdu University, Chengdu 610106, China [6]School of Food and Biological Engineering, Chengdu University, Chengdu 610106, China

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通讯作者：

通讯机构： [1]Engineering Research Center of Sichuan-Tibet Traditional Medicinal Plant, Chengdu University, Chengdu 610106, China [2]Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, NO. 110, Ganhe Road, Shanghai 200437, China [3]Institute of Cancer Biology and Drug Discovery, Chengdu University, Chengdu 610106, China [4]School of Basic Medical Sciences, Chengdu University, NO. 2025, Chengluo Road, Chengdu 610106, China [*1]School of Basic Medical Sciences, Chengdu University, NO. 2025, Chengluo Road, Chengdu 610106, China

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Phellopterin alleviates atopic dermatitis-like inflammation and suppresses IL-4-induced STAT3 activation in keratinocytes

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