High-Throughput Identification of Epigenetic Compounds to Enhance Chicken Host Defense Peptide Gene Expression

文献类型： 外文期刊

第一作者： Deng, Zhuo

作者： Deng, Zhuo;Lyu, Wentao;Zhang, Guolong;Lyu, Wentao;Deng, Zhuo

作者机构：

关键词： antimicrobial resistance; antibiotic alternatives; host defense peptides; host defense peptide inducers; high throughput screening; histone deacetylase inhibitors; entinostat; chickens

期刊名称：ANTIBIOTICS-BASEL （ 影响因子：5.222； 五年影响因子：5.396 ）

ISSN： 2079-6382

年卷期： 2022 年 11 卷 7 期

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收录情况： SCI

摘要： Enhancing the synthesis of endogenous host defense peptides (HDPs) has emerged as a novel antibiotic-free approach to infectious disease control and prevention. A number of epigenetic compounds have been identified as HDP inducers and several have proved beneficial in antimicrobial therapy. However, species-specific regulation of HDP synthesis is evident. In attempt to identify epigenetic compounds with potent HDP-inducing activity for poultry-specific application, we developed a stable luciferase reporter cell line, known as HTC/AvBD10-luc, following our earlier construction of HTC/AvBD9-luc. HTC/AvBD10-luc was developed through permanent integration of a chicken macrophage cell line, HTC, with a lentiviral luciferase reporter vector driven by a 4-Kb AvBD10 gene promoter. Using a high throughput screening assay based on the two stable cell lines, we identified 33 hits, mostly being histone deacetylase (HDAC) inhibitors, from a library of 148 epigenetic compounds. Among them, entinostat and its structural analog, tucidinostat, were particularly effective in promoting multiple HDP gene expression in chicken macrophages and jejunal explants. Desirably, neither compounds triggered an inflammatory response. Moreover, oral gavage of entinostat significantly enhanced HDP gene expression in the chicken intestinal tract. Collectively, the high throughput assay proves to be effective in identifying HDP inducers, and both entinostat and tucidinostat could be potentially useful as alternatives to antibiotics to enhance intestinal immunity and disease resistance.

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