title: NLRP3 Activation Was Regulated by DNA Methylation Modification during Mycobacterium tuberculosis Infection.
abstract: 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.
authors.affiliation: School of Life Science, Institute of Neurobiology and Anhui Key Laboratory of Infection and Immunity, Bengbu Medical College, Bengbu 233030, China.
authors.forename: Meili
authors.initials: M
authors.lastname: Wei
authors.affiliation: School of Life Science, Institute of Neurobiology and Anhui Key Laboratory of Infection and Immunity, Bengbu Medical College, Bengbu 233030, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.affiliation: School of Life Science, Institute of Neurobiology and Anhui Key Laboratory of Infection and Immunity, Bengbu Medical College, Bengbu 233030, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wu
authors.affiliation: School of Life Science, Institute of Neurobiology and Anhui Key Laboratory of Infection and Immunity, Bengbu Medical College, Bengbu 233030, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Xi
authors.affiliation: School of Life Science, Institute of Neurobiology and Anhui Key Laboratory of Infection and Immunity, Bengbu Medical College, Bengbu 233030, China.
authors.forename: Yuze
authors.initials: Y
authors.lastname: Han
authors.affiliation: School of Life Science, Institute of Neurobiology and Anhui Key Laboratory of Infection and Immunity, Bengbu Medical College, Bengbu 233030, China.
authors.forename: Xingxiang
authors.initials: X
authors.lastname: Yang
authors.affiliation: School of Life Science, Institute of Neurobiology and Anhui Key Laboratory of Infection and Immunity, Bengbu Medical College, Bengbu 233030, China.
authors.forename: Ding
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Microbiology and Parasitology, Anhui Key Laboratory of Infection and Immunity, Bengbu Medical College, Bengbu 233030, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Fang
authors.affiliation: School of Life Science, Institute of Neurobiology and Anhui Key Laboratory of Infection and Immunity, Bengbu Medical College, Bengbu 233030, China.
authors.forename: Bikui
authors.identifier: 0000-0003-1854-229X
authors.initials: B
authors.lastname: Tang
mesh_terms: D002460:Cell Line; D016207:Cytokines / Q000235:genetics; D019175:DNA Methylation; D015257:DNA-Cytosine Methylases / Q000378:metabolism; D054884:Host-Pathogen Interactions / Q000235:genetics; D006801:Humans; D058847:Inflammasomes / Q000235:genetics / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000235:genetics* / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014376:Tuberculosis / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*
chemical_list: D016207:Cytokines; D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D012333:RNA, Messenger; C081573:DNA modification methylase SssI; D015257:DNA-Cytosine Methylases