Wei Meili, Wang Lu, Wu Tao, Xi Jun, Han Yuze, Yang Xingxiang, Zhang Ding, Fang Qiang, Tang Bikui
School of Life Science, Institute of Neurobiology and Anhui Key Laboratory of Infection and Immunity, Bengbu Medical College, Bengbu 233030, China.
Department of Microbiology and Parasitology, Anhui Key Laboratory of Infection and Immunity, Bengbu Medical College, Bengbu 233030, China.
Biomed Res Int. 2016;2016:4323281. doi: 10.1155/2016/4323281. Epub 2016 Jun 6.
Mycobacterium tuberculosis (Mtb) infection activates the NLRP3 inflammasome in macrophages and dendritic cells. Much attention has been paid to the mechanisms for regulation of NLRP3 against Mtb. However, whether epigenetic mechanisms participated in NLRP3 activation is still little known. Here we showed that NLRP3 activation was regulated by DNA methylation modification. Mtb infection promoted NLRP3 activation and inflammatory cytokines expression. NLRP3 promoter was cloned and subsequently identified by Dual-Luciferase Reporter System. The results showed that NLRP3 promoter activity was decreased after methylation by DNA methylase Sss I in vitro. Meanwhile, DNA methyltransferases inhibitor DAC could upregulate the expression of NLRP3. Furthermore, promoter region of NLRP3 gene was demethylated after Mtb H37Rv strain infection. These data revealed that DNA methylation was involved in NLRP3 inflammasome activation during Mtb infection and provided a new insight into the relationship between host and pathogens.
结核分枝杆菌（Mtb）感染可激活巨噬细胞和树突状细胞中的NLRP3炎性小体。人们对NLRP3抗Mtb的调控机制给予了诸多关注。然而，表观遗传机制是否参与NLRP3激活仍鲜为人知。在此我们表明，NLRP3激活受DNA甲基化修饰调控。Mtb感染促进NLRP3激活和炎性细胞因子表达。克隆NLRP3启动子，随后通过双荧光素酶报告系统进行鉴定。结果显示，体外经DNA甲基化酶Sss I甲基化后，NLRP3启动子活性降低。同时，DNA甲基转移酶抑制剂DAC可上调NLRP3的表达。此外，Mtb H37Rv菌株感染后，NLRP3基因的启动子区域发生去甲基化。这些数据表明，DNA甲基化参与了Mtb感染期间NLRP3炎性小体的激活，并为宿主与病原体之间的关系提供了新的见解。
