Recent studies suggest that microbiome derived 3(3,4-dihydroxy-phenyl) propionic acid (DHCA) attenuates IL-6 cytokine production through downregulation of the epigenetic modifier DNA Methyltransferase 1 (DNMT1) expression and inhibition of DNA methylation at the 5′—C—phosphate—G—3′ (CpG)-rich IL6 sequence introns 1 and 3 in a mouse model of depression. In this study, we extended the investigation of DHCA epigenetic mechanisms in IL-6 expression in human peripheral blood mononuclear cells (PBMC). Using Lucia Luciferase reporter gene system we identified CpG-rich sequences in which of methylation is influenced by DHCA similar to what observed in response to treatment with the DNA methylation inhibitor 5-aza-2′-deoxycytidine. Correlation study showed that DNA methylation at select CpG motifs in the IL-6 promoter correlates with IL-6 gene expression. Our study suggests that DHCA is effective in reducing IL-6 expression in human PBMCs, in part, by regulation of methylation in the IL-6 promoter region.

最近的研究表明，微生物组衍生的 3(3,4-二羟基-苯基)丙酸 (DHCA) 通过下调表观遗传修饰剂 DNA 甲基转移酶 1 (DNMT1) 的表达和抑制 5' 处的 DNA 甲基化来减弱 IL-6 细胞因子的产生—— C-磷酸盐-G-3' (CpG) 富含 IL6 序列内含子 1 和 3 在抑郁症小鼠模型中。在这项研究中，我们扩展了对人外周血单核细胞 (PBMC) 中 IL-6 表达的 DHCA 表观遗传机制的研究。使用露西亚荧光素酶报告基因系统我们鉴定了富含 CpG 的序列，其中甲基化受 DHCA 的影响类似于在用 DNA 甲基化抑制剂 5-aza-2'-deoxycytidine 处理时观察到的。相关性研究表明，IL-6 启动子中选定 CpG 基序的 DNA 甲基化与 IL-6 基因表达相关。我们的研究表明，DHCA 可有效降低人 PBMC 中 IL-6 的表达，部分原因是通过调节 IL-6 启动子区域的甲基化。