RRC ID 18192
Author Seong AR, Yoo JY, Choi K, Lee MH, Lee YH, Lee J, Jun W, Kim S, Yoon HG.
Title Delphinidin, a specific inhibitor of histone acetyltransferase, suppresses inflammatory signaling via prevention of NF-κB acetylation in fibroblast-like synoviocyte MH7A cells.
Journal Biochem Biophys Res Commun
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.
Volume 410(3)
Pages 581-6
Published 2011-7-8
DOI 10.1016/j.bbrc.2011.06.029
PII S0006-291X(11)00987-9
PMID 21683061
MeSH Acetylation / drug effects Anthocyanins / pharmacology* Anti-Inflammatory Agents, Non-Steroidal / pharmacology* Arthritis / genetics Arthritis / immunology* Cell Line Cytokines / antagonists & inhibitors* Enzyme Inhibitors / pharmacology* Fibroblasts / drug effects Fibroblasts / metabolism Gene Expression / drug effects Gene Expression / genetics Histone Acetyltransferases / antagonists & inhibitors* Humans Jurkat Cells NF-kappa B / metabolism* Synovial Fluid / drug effects Synovial Fluid / metabolism
IF 2.705
Times Cited 45
WOS Category BIOPHYSICS BIOCHEMISTRY & MOLECULAR BIOLOGY
Resource
Human and Animal Cells MH7A (RCB1512)