title: The regulation of Jmjd3 upon the expression of NF-κB downstream inflammatory genes in LPS activated vascular endothelial cells.
abstract: Inflammatory mediators and adhesion molecules have been implicated in a variety of diseases including atherosclerosis. As both the mediator-releasing and targeted cells, vascular endothelial cells play key role in pathological processes. NF-κB signaling regulates a cluster of inflammatory factors in LPS-activated vascular endothelial cells but the underlying mechanisms remain largely unknown. Here, we investigated the epigenetic regulation of LPS upon the expression of inflammatory mediators and adhesion molecules. We found that LPS treatment promoted jmjd3 expression, enhanced Jmjd3 nuclear accumulation in human vascular endothelial cells. In addition, LPS enhanced the demethylation of H3K27me3, a specific substrate of Jmjd3. LPS treatment recruited Jmjd3 and NF-κB to the promoter region of target genes, suggesting Jmjd3 synergizes with NF-κB to activate the expression of target genes. We further found that Jmjd3 attenuated the methylation status in promoter region of target genes, culminating in target gene expression. Our findings unveil epigenetic regulations of LPS upon NF-κB pathway and identify Jmjd3 as a critical modulator of NF-κB pathway and potential therapeutic target for NF-κB related diseases including atherosclerosis.
authors.affiliation: Burn Center, The First Affiliated Hospital of Nanchang University, Nanchang, China; Graduate School of Medicine, Nanchang University, Nanchang, China.
authors.forename: Shaoqing
authors.initials: S
authors.lastname: Yu
authors.affiliation: Graduate School of Medicine, Nanchang University, Nanchang, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Chen
authors.affiliation: Burn Center, The First Affiliated Hospital of Nanchang University, Nanchang, China.
authors.forename: Min
authors.initials: M
authors.lastname: Xiu
authors.affiliation: Burn Center, The First Affiliated Hospital of Nanchang University, Nanchang, China.
authors.forename: Feng
authors.initials: F
authors.lastname: He
authors.affiliation: Burn Center, The First Affiliated Hospital of Nanchang University, Nanchang, China.
authors.forename: Juanjuan
authors.initials: J
authors.lastname: Xing
authors.affiliation: Burn Center, The First Affiliated Hospital of Nanchang University, Nanchang, China.
authors.forename: Dinghong
authors.initials: D
authors.lastname: Min
authors.affiliation: Burn Center, The First Affiliated Hospital of Nanchang University, Nanchang, China. Electronic address: guofei2005@126.com.
authors.forename: Fei
authors.initials: F
authors.lastname: Guo
mesh_terms: D015815:Cell Adhesion Molecules / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D042783:Endothelial Cells / Q000276:immunology* / Q000378:metabolism; D044127:Epigenesis, Genetic; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology; D056484:Jumonji Domain-Containing Histone Demethylases / Q000032:analysis / Q000235:genetics* / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology*; D016328:NF-kappa B / Q000276:immunology*; D011401:Promoter Regions, Genetic; D015854:Up-Regulation
chemical_list: D015815:Cell Adhesion Molecules; D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; D056484:Jumonji Domain-Containing Histone Demethylases; C524220:KDM6B protein, human
keywords: H3K27; Inflammation; Jmjd3; NF-κB; Vascular endothelial cell