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FlavopiridolnProtects against Fungal Keratitis duento Aspergillus fumigatus by AlleviatingnInflammation through the Promotion of Autophagy 黄吡醇通过促进自噬减轻炎症，预防烟曲霉引起的真菌性角膜炎

Figshare Pub Date : 2022-10-25 DOI: 10.1021/acsinfecdis.2c00427.s001

Lingwen Gu (14009553), Cui Li (160318), Xudong Peng (794380), Hao Lin (123504), Yawen Niu (14009556), Hengrui Zheng (811829), Guiqiu Zhao (400745), Jing Lin (50818)

{"title":"FlavopiridolnProtects against Fungal Keratitis duento Aspergillus fumigatus by AlleviatingnInflammation through the Promotion of Autophagy","authors":"Lingwen Gu (14009553), Cui Li (160318), Xudong Peng (794380), Hao Lin (123504), Yawen Niu (14009556), Hengrui Zheng (811829), Guiqiu Zhao (400745), Jing Lin (50818)","doi":"10.1021/acsinfecdis.2c00427.s001","DOIUrl":"https://doi.org/10.1021/acsinfecdis.2c00427.s001","url":null,"abstract":"Fungalnkeratitis is a serious infectious keratopathy related tonfungal virulence and excessive inflammatory responses. Autophagy exhibitsna potent ability to resolve inflammation during fungal infection.nThis study aimed to investigate the protective function of flavopiridolnin Aspergillus fumigatus keratitisnand explore its effects on autophagy. In our study, the corneas ofnthe fungal keratitis mouse model were treated with 5 μM flavopiridol. <i>In vitro</i>, RAW 264.7 cells were pretreated with 200 nM flavopiridolnbefore fungal stimulation. A. fumigatus was incubated with flavopiridol, and the antifungal activity ofnflavopiridol was detected. Our results indicated that flavopiridolntreatment notably reduced clinical scores as well as cytokines expressionnof infected corneas. In infected RAW 264.7 cells, flavopiridol treatmentninhibited IL-1β, IL-6, and TNF-α expression but promotednIL-10 expression. Transmission electron microscopy (TEM) images showednthat more autolysosomes were present in infected corneas and RAW 264.7ncells after flavopiridol treatment. Flavopiridol treatment notablynupregulated the protein expression of LC3, Beclin-1, and Atg-7. 3-Methyladeninen(3-MA, an inhibitor of autophagy) pretreatment counteracted the cytokinenregulation induced by flavopiridol. Moreover, flavopiridol promotednthe phagocytosis of RAW 264.7 cells. Flavopiridol also exhibited antifungalnactivity by restricting fungal growth and limiting fungal biofilmnformation and conidial adhesion. In conclusion, flavopiridol significantlynalleviated the inflammation of fungal keratitis by activating autophagy.nIn addition, flavopiridol promoted the phagocytosis of RAW 264.7 cellsnand exhibited antifungal function, indicating the potential therapeuticnrole of flavopiridol in fungal keratitis.","PeriodicalId":523331,"journal":{"name":"Figshare","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147914187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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