{"title":"Topical histone deacetylase inhibitor remetinostat improves IMQ-induced psoriatic dermatitis via suppressing dendritic cell maturation and keratinocyte differentiation and inflammation","authors":"","doi":"10.1016/j.ejphar.2024.177011","DOIUrl":null,"url":null,"abstract":"<div><div>Psoriasis is a chronic inflammatory skin disease characterized by excessive proliferation of keratinocytes and infiltration of immune cells. Although psoriasis has entered the era of biological treatment, there is still a need to explore more effective therapeutic targets and drugs due to the presence of resistance and adverse reactions to biologics. Remetinostat, an HDAC inhibitor, can maintain its potency within the skin with minimal systemic effects, making it a promising topical medication for treating psoriasis. But its effectiveness in treating psoriasis has not been evaluated. In this study, the topical application of remetinostat significantly improved psoriasiform inflammation in an imiquimod-induced mice model by inhibiting CD86 expression of CD11C<sup>+</sup>I-A/I-E<sup>+</sup> dendritic cells (DCs) in the skin. Moreover, remetinostat could dampen the maturation and activation of bone marrow-derived DCs in vitro, as well as the expression of psoriasis-related inflammatory mediators by keratinocytes. In addition, remetinostat could promote keratinocyte differentiation without affecting its proliferation. Our findings demonstrate that remetinostat improves psoriasis by inhibiting the maturation and activation of DCs and the differentiation and inflammation of keratinocytes, which may facilitate the potential application of remetinostat in anti-psoriasis therapy.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":null,"pages":null},"PeriodicalIF":4.2000,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"European journal of pharmacology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0014299924007015","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
Abstract
Psoriasis is a chronic inflammatory skin disease characterized by excessive proliferation of keratinocytes and infiltration of immune cells. Although psoriasis has entered the era of biological treatment, there is still a need to explore more effective therapeutic targets and drugs due to the presence of resistance and adverse reactions to biologics. Remetinostat, an HDAC inhibitor, can maintain its potency within the skin with minimal systemic effects, making it a promising topical medication for treating psoriasis. But its effectiveness in treating psoriasis has not been evaluated. In this study, the topical application of remetinostat significantly improved psoriasiform inflammation in an imiquimod-induced mice model by inhibiting CD86 expression of CD11C+I-A/I-E+ dendritic cells (DCs) in the skin. Moreover, remetinostat could dampen the maturation and activation of bone marrow-derived DCs in vitro, as well as the expression of psoriasis-related inflammatory mediators by keratinocytes. In addition, remetinostat could promote keratinocyte differentiation without affecting its proliferation. Our findings demonstrate that remetinostat improves psoriasis by inhibiting the maturation and activation of DCs and the differentiation and inflammation of keratinocytes, which may facilitate the potential application of remetinostat in anti-psoriasis therapy.
期刊介绍:
The European Journal of Pharmacology publishes research papers covering all aspects of experimental pharmacology with focus on the mechanism of action of structurally identified compounds affecting biological systems.
The scope includes:
Behavioural pharmacology
Neuropharmacology and analgesia
Cardiovascular pharmacology
Pulmonary, gastrointestinal and urogenital pharmacology
Endocrine pharmacology
Immunopharmacology and inflammation
Molecular and cellular pharmacology
Regenerative pharmacology
Biologicals and biotherapeutics
Translational pharmacology
Nutriceutical pharmacology.