title: Delphinidin, a specific inhibitor of histone acetyltransferase, suppresses inflammatory signaling via prevention of NF-κB acetylation in fibroblast-like synoviocyte MH7A cells.
abstract: Histone acetyltransferase (HAT) inhibitors (HATi) isolated from dietary compounds have been shown to suppress inflammatory signaling, which contributes to rheumatoid arthritis. Here, we identified a novel HATi in Punica granatum L. known as delphinidin (DP). DP did not affect the activity of other epigenetic enzymes (histone deacetylase, histone methyltransferase, or sirtuin1). DP specifically inhibited the HAT activities of p300/CBP. It also inhibited p65 acetylation in MH7A cells, a human rheumatoid arthritis synovial cell line. DP-induced hypoacetylation was accompanied by cytosolic accumulation of p65 and nuclear localization of IKBα. Accordingly, DP treatment inhibited TNFα-stimulated increases in NF-κB function and expression of NF-κB target genes in these cells. Importantly, DP suppressed lipopolysaccharide-induced pro-inflammatory cytokine expression in Jurkat T lymphocytes, demonstrating that HATi efficiently suppresses cytokine-mediated immune responses. Together, these results show that the HATi activity of DP counters anti-inflammatory signaling by blocking p65 acetylation and that this compound may be useful in preventing inflammatory arthritis.
authors.affiliation: Department of Biochemistry and Molecular Biology, Center for Chronic Metabolic Disease Research, College of Medicine, Yonsei University, Seoul, South Korea.
authors.forename: Ah-Reum
authors.initials: AR
authors.lastname: Seong
authors.forename: Jung-Yoon
authors.initials: JY
authors.lastname: Yoo
authors.forename: KyungChul
authors.initials: K
authors.lastname: Choi
authors.forename: Mee-Hee
authors.initials: MH
authors.lastname: Lee
authors.forename: Yoo-Hyun
authors.initials: YH
authors.lastname: Lee
authors.forename: Jeongmin
authors.initials: J
authors.lastname: Lee
authors.forename: Woojin
authors.initials: W
authors.lastname: Jun
authors.forename: Sunoh
authors.initials: S
authors.lastname: Kim
authors.forename: Ho-Geun
authors.initials: HG
authors.lastname: Yoon
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000872:Anthocyanins / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001168:Arthritis / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D016207:Cytokines / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D051548:Histone Acetyltransferases / Q000037:antagonists & inhibitors*; D006801:Humans; D019169:Jurkat Cells; D016328:NF-kappa B / Q000378:metabolism*; D013582:Synovial Fluid / Q000187:drug effects / Q000378:metabolism
chemical_list: D000872:Anthocyanins; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D004791:Enzyme Inhibitors; D016328:NF-kappa B; D051548:Histone Acetyltransferases; C017185:delphinidin