Ye-Hao Liang , Peng Shu , Yong-Liang Li , Menggeng Li , Zi-Heng Ye , Shanpeng Chu , Zhi-Yun Du , Chang-Zhi Dong , Bernard Meunier , Hui-Xiong Chen
{"title":"GDU-952是一种新型AhR激动剂，可改善DNFB诱导的小鼠特应性皮炎的皮肤屏障异常和免疫功能障碍。","authors":"Ye-Hao Liang , Peng Shu , Yong-Liang Li , Menggeng Li , Zi-Heng Ye , Shanpeng Chu , Zhi-Yun Du , Chang-Zhi Dong , Bernard Meunier , Hui-Xiong Chen","doi":"10.1016/j.bcp.2023.115835","DOIUrl":null,"url":null,"abstract":"<div><p><span><span>The aryl hydrocarbon receptor (AhR) is widely expressed in the skin. It controls immune-mediated skin responses to various external environmental signals, promote terminal differentiation of epidermal keratinocytes and participates the maintenance of the skin barrier function. As a therapeutic target, AhR activation modulates many </span>diseases progression<span><span> driven by immune/inflammatory processes such as atopic dermatitis (AD) and </span>psoriasis. In this study, we revealed that GDU-952 is a novel AhR agonist, which is able to decreases IgE serum levels, to inhibit pro-inflammatory cytokines such as IL-6 and TNF-α and to induce immunoregulatory effects through restoring Th1/Th2 immune balance and promoting CD4</span></span><sup>+</sup>FOXP3<sup>+</sup><span><span>regulatory T (Treg) populations in AD skin lesions<span>. Furthermore, GDU-952 can strengthen the skin barrier function through upregulating epidermal differentiation-related and tight junction proteins. This may alleviate AD symptoms, such as dermatitis scores, </span></span>epidermal hyperplasia and mast cell infiltration. These results offer a rationale for further preclinical/clinical studies to evaluate the possible use of GDU-952 in the management of AD.</span></p></div>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":"217 ","pages":"Article 115835"},"PeriodicalIF":5.6000,"publicationDate":"2023-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"GDU-952, a novel AhR agonist ameliorates skin barrier abnormalities and immune dysfunction in DNFB-induced atopic dermatitis in mice\",\"authors\":\"Ye-Hao Liang , Peng Shu , Yong-Liang Li , Menggeng Li , Zi-Heng Ye , Shanpeng Chu , Zhi-Yun Du , Chang-Zhi Dong , Bernard Meunier , Hui-Xiong Chen\",\"doi\":\"10.1016/j.bcp.2023.115835\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p><span><span>The aryl hydrocarbon receptor (AhR) is widely expressed in the skin. It controls immune-mediated skin responses to various external environmental signals, promote terminal differentiation of epidermal keratinocytes and participates the maintenance of the skin barrier function. As a therapeutic target, AhR activation modulates many </span>diseases progression<span><span> driven by immune/inflammatory processes such as atopic dermatitis (AD) and </span>psoriasis. In this study, we revealed that GDU-952 is a novel AhR agonist, which is able to decreases IgE serum levels, to inhibit pro-inflammatory cytokines such as IL-6 and TNF-α and to induce immunoregulatory effects through restoring Th1/Th2 immune balance and promoting CD4</span></span><sup>+</sup>FOXP3<sup>+</sup><span><span>regulatory T (Treg) populations in AD skin lesions<span>. Furthermore, GDU-952 can strengthen the skin barrier function through upregulating epidermal differentiation-related and tight junction proteins. This may alleviate AD symptoms, such as dermatitis scores, </span></span>epidermal hyperplasia and mast cell infiltration. These results offer a rationale for further preclinical/clinical studies to evaluate the possible use of GDU-952 in the management of AD.</span></p></div>\",\"PeriodicalId\":8806,\"journal\":{\"name\":\"Biochemical pharmacology\",\"volume\":\"217 \",\"pages\":\"Article 115835\"},\"PeriodicalIF\":5.6000,\"publicationDate\":\"2023-09-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biochemical pharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0006295223004264\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biochemical pharmacology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0006295223004264","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
GDU-952, a novel AhR agonist ameliorates skin barrier abnormalities and immune dysfunction in DNFB-induced atopic dermatitis in mice
The aryl hydrocarbon receptor (AhR) is widely expressed in the skin. It controls immune-mediated skin responses to various external environmental signals, promote terminal differentiation of epidermal keratinocytes and participates the maintenance of the skin barrier function. As a therapeutic target, AhR activation modulates many diseases progression driven by immune/inflammatory processes such as atopic dermatitis (AD) and psoriasis. In this study, we revealed that GDU-952 is a novel AhR agonist, which is able to decreases IgE serum levels, to inhibit pro-inflammatory cytokines such as IL-6 and TNF-α and to induce immunoregulatory effects through restoring Th1/Th2 immune balance and promoting CD4+FOXP3+regulatory T (Treg) populations in AD skin lesions. Furthermore, GDU-952 can strengthen the skin barrier function through upregulating epidermal differentiation-related and tight junction proteins. This may alleviate AD symptoms, such as dermatitis scores, epidermal hyperplasia and mast cell infiltration. These results offer a rationale for further preclinical/clinical studies to evaluate the possible use of GDU-952 in the management of AD.
期刊介绍：
Biochemical Pharmacology publishes original research findings, Commentaries and review articles related to the elucidation of cellular and tissue function(s) at the biochemical and molecular levels, the modification of cellular phenotype(s) by genetic, transcriptional/translational or drug/compound-induced modifications, as well as the pharmacodynamics and pharmacokinetics of xenobiotics and drugs, the latter including both small molecules and biologics.
The journal''s target audience includes scientists engaged in the identification and study of the mechanisms of action of xenobiotics, biologics and drugs and in the drug discovery and development process.
All areas of cellular biology and cellular, tissue/organ and whole animal pharmacology fall within the scope of the journal. Drug classes covered include anti-infectives, anti-inflammatory agents, chemotherapeutics, cardiovascular, endocrinological, immunological, metabolic, neurological and psychiatric drugs, as well as research on drug metabolism and kinetics. While medicinal chemistry is a topic of complimentary interest, manuscripts in this area must contain sufficient biological data to characterize pharmacologically the compounds reported. Submissions describing work focused predominately on chemical synthesis and molecular modeling will not be considered for review.
While particular emphasis is placed on reporting the results of molecular and biochemical studies, research involving the use of tissue and animal models of human pathophysiology and toxicology is of interest to the extent that it helps define drug mechanisms of action, safety and efficacy.
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