title: Changes in DNA Methylation and Chromatin Structure of Pro-inflammatory Cytokines Stimulated by LPS in Broiler Peripheral Blood Mononuclear Cells.
abstract: The pro-inflammatory cytokines IL-1β, IL-6, and tumor necrosis factor (TNF)-α mediate inflammation, which is a protective response by body to ensure removal of detrimental stimuli, as well as a healing process for repairing damaged tissue. The overproduction of pro-inflammatory cytokines can induce autoimmune diseases and can be fatal. The aim of this study was to investigate epigenetic mechanisms in the regulation of pro-inflammatory cytokines expression after lipopolysaccharide (LPS) stimulation of broiler peripheral blood mononuclear cells (PBMC). Gene expression, promoter DNA methylation, and chromatin accessibility of pro-inflammatory cytokines in untreated and LPS-treated PBMC were compared. The expression of epigenetic enzymes DNA methyltransferase (DNMT) 1, histone deacetylase (HDAC), and histone acetylase (HAT) were measured after LPS stimulation. The results showed the activated gene expression of pro-inflammatory cytokines in broiler PBMC stimulated 3 h by LPS. The demethylation of IL-6 gene - 302 and -264 cytosine-guanine (CpG) sites, as well as TNF-α gene -371 CpG site, occurred after LPS treatment (P < 0.05), whereas the methylaiton pattern in the IL-1β gene promoter region was not affected. Otherwise, LPS stimulation relaxed the chromatin structure at IL-1β and IL-6 promoter (P < 0.05). The lower expression of DNMT1 and HDAC2, and higher expression of p300-CBP-associated factor and tat-interaction protein-60, were detected in response to LPS (P < 0.05). Our data indicated that after LPS stimulation for 3 h, IL-1β and IL-6 promoter are remodeled into an accessible structure, and the IL-6 and TNF-α promoter are demethylated at special sites, which possible impact the mRNA expression of pro-inflammatory cytokines.
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, P. R. of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Shen
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, P. R. of China.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Liu
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, P. R. of China.
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Ren
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, P. R. of China.
authors.forename: Kang
authors.initials: K
authors.lastname: Gao
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, P. R. of China.
authors.forename: Yulong
authors.initials: Y
authors.lastname: Li
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, P. R. of China.
authors.forename: Shizhao
authors.initials: S
authors.lastname: Li
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, P. R. of China.
authors.forename: Junhu
authors.initials: J
authors.lastname: Yao
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, P. R. of China. Electronic address: yangxj@nwsuaf.edu.cn.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Yang
mesh_terms: D000818:Animals; D030161:Avian Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D002645:Chickens / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D002843:Chromatin / Q000737:chemistry*; D016207:Cytokines / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male
chemical_list: D030161:Avian Proteins; D002843:Chromatin; D016207:Cytokines; D008070:Lipopolysaccharides
keywords: DNA methylation; broiler peripheral blood mononuclear cells; chromatin accessibility; gene regulation; pro-inflammatory cytokine