Ultraviolet-treated riboflavin alleviates atopic dermatitis by inhibiting NLRP3 inflammasome activation and M1 macrophage polarization via histone lactylation

IF 5.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

Biochemical pharmacology Pub Date : 2025-03-19 DOI:10.1016/j.bcp.2025.116879

Shuang Ge , Bingquan Qiu , Ruining Liu , Liping Sun , Lu Yang , Xinghui Chen , Hongjin Tao , Wei Yang , Yang Yu , Deqing Wang

{"title":"Ultraviolet-treated riboflavin alleviates atopic dermatitis by inhibiting NLRP3 inflammasome activation and M1 macrophage polarization via histone lactylation","authors":"Shuang Ge , Bingquan Qiu , Ruining Liu , Liping Sun , Lu Yang , Xinghui Chen , Hongjin Tao , Wei Yang , Yang Yu , Deqing Wang","doi":"10.1016/j.bcp.2025.116879","DOIUrl":null,"url":null,"abstract":"<div><div>Atopic dermatitis (AD) is a chronic inflammatory skin disorder requiring improved therapeutic strategies. This study investigates the potential of ultraviolet (UV)-treated riboflavin in AD treatment. Using a MC903-induced mouse model, we demonstrate that topical UV-treated riboflavin significantly attenuates AD progression. Mechanistically, UV-treated riboflavin suppresses macrophage nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation by reducing histone H3 lysine 9 lactylation (H3K9la) on NLRP3 and apoptosis-associated speck-like protein containing a CARD (ASC) promoter, decreasing interleukin-1β (IL-1β) secretion and subsequent keratinocyte-derived thymic stromal lymphopoietin (TSLP) production. It also directly inhibits inflammatory cytokine expression in keratinocytes. NLRP3 activation in vivo partially reverses these effects, confirming the central role of NLRP3 inflammasome inhibition. Our findings reveal a novel epigenetic mechanism of UV-treated riboflavin in modulating immune responses in AD, highlighting its potential as a therapeutic strategy for inflammatory skin disorders.</div></div>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":"236 ","pages":"Article 116879"},"PeriodicalIF":5.3000,"publicationDate":"2025-03-19","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/S0006295225001418","RegionNum":2,"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

Atopic dermatitis (AD) is a chronic inflammatory skin disorder requiring improved therapeutic strategies. This study investigates the potential of ultraviolet (UV)-treated riboflavin in AD treatment. Using a MC903-induced mouse model, we demonstrate that topical UV-treated riboflavin significantly attenuates AD progression. Mechanistically, UV-treated riboflavin suppresses macrophage nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation by reducing histone H3 lysine 9 lactylation (H3K9la) on NLRP3 and apoptosis-associated speck-like protein containing a CARD (ASC) promoter, decreasing interleukin-1β (IL-1β) secretion and subsequent keratinocyte-derived thymic stromal lymphopoietin (TSLP) production. It also directly inhibits inflammatory cytokine expression in keratinocytes. NLRP3 activation in vivo partially reverses these effects, confirming the central role of NLRP3 inflammasome inhibition. Our findings reveal a novel epigenetic mechanism of UV-treated riboflavin in modulating immune responses in AD, highlighting its potential as a therapeutic strategy for inflammatory skin disorders.

Abstract Image

查看原文本刊更多论文

求助全文

约1分钟内获得全文求助全文

来源期刊

Biochemical pharmacology 医学-药学

CiteScore

10.30

自引率

1.70%

发文量

420

审稿时长

17 days

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.