Epigenetic modulation of cytokine expression in Mycobacterium tuberculosis-infected monocyte derived-dendritic cells: Implications for tuberculosis diagnosis

DNA甲基化 甲基化 表观遗传学 结核分枝杆菌 生物 基因 基因表达 发起人 分子生物学 细胞因子 肿瘤坏死因子α 聚合酶链反应 肺结核 免疫学 遗传学 医学 病理
作者
Maryam Meskini,Mohammad Saber Zamani,Amir Amanzadeh,Saeid Bouzari,Morteza Karimipoor,Andrea Fuso,Abolfazl Fateh,Seyed Davar Siadat
出处
期刊:Cytokine [Elsevier BV]
卷期号:181: 156693-156693
标识
DOI:10.1016/j.cyto.2024.156693
摘要

To delineate alterations in DNA methylation at high resolution within the genomic profile of monocyte-derived-dendritic cells (mo-DCs) in connection with Mycobacterium tuberculosis (MTB) infection, with particular emphasis on pro/ anti-inflammatory genes. In the context of this investigation, mo-DCs were infected by various active strains of MTB (Rifampicin-resistant [RIFR], H37Rv, multidrug-resistant [MDR], and extensively drug-resistant [XDR]). Subsequently, the pro/anti-inflammatory hub gene expression levels within the IL-6, IL-12, IFN-γ, IL-1β, TNF-α, and IL-10 pathways were evaluated employing real-time reverse transcription–polymerase chain reaction (RT-PCR). Additionally, the effects of MTB infection on mo-DC protein expression were examined through western blot analysis. The methylation status (%) of TNF-α and IL-10 was considered through Methylation Sensitive-High Resolution Melting (MS-HRM). The results revealed an up-regulation of all pro-inflammatory genes among all groups, with TNF-α exhibiting the highest expression level. Conversely, the anti-inflammatory gene (IL-10) showed a down-regulated expression level. Furthermore, the DNA methylation status (%) of TNF-α decreased significantly among all the groups (P < 0.001), although there were no notable distinctions in the DNA methylation status (%) of IL-10 when compared to the control group (P > 0.05). MTB infection induces DNA methylation changes in mo-DCs. The hypo-methylation of TNF-α may induce the up-regulation of this gene. This correlation revealed that the more resistant the MTB strain (XDR) is, the lower the methylation status (%) in the TNF-α gene.
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