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Title: Delphinidin, a specific inhibitor of histone acetyltransferase, suppresses inflammatory signaling via prevention of NF-{kappa}B acetylation in fibroblast-like synoviocyte MH7A cells

Highlights: {yields} Delphinidin is a novel inhibitor of p300/CBP histone acetyltransferase. {yields} Delphinidin prevents the hyperacetylation of p65 by inhibiting the HAT activity of p300/CBP. {yields} Delphinidin efficiently suppresses the expression of inflammatory cytokines in MH7A cells via hypoacetylation of NF-{kappa}B. {yields} Delphinidin inhibits cytokine release in the Jurkat T lymphocyte cell line. -- 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 IKB{alpha}. Accordingly, DP treatment inhibited TNF{alpha}-stimulated increases in NF-{kappa}B function and expression of NF-{kappa}B 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 thismore » compound may be useful in preventing inflammatory arthritis.« less
Authors:
; ;  [1] ;  [1] ;  [2] ;  [3] ;  [4] ;  [5] ;  [6] ;  [1] ;  [2]
  1. Department of Biochemistry and Molecular Biology, Center for Chronic Metabolic Disease Research, College of Medicine, Yonsei University, Seoul (Korea, Republic of)
  2. (Korea, Republic of)
  3. Department of Food Science and Nutrition, The University of Suwon, Kyunggi-do (Korea, Republic of)
  4. Department of Medical Nutrition, Kyung Hee University, Kyunggi-do (Korea, Republic of)
  5. Department of Food and Nutrition, Chonnam National University, Gwangju (Korea, Republic of)
  6. Jeollanamdo Institute of Natural Resources Research, Jeonnam (Korea, Republic of)
Publication Date:
OSTI Identifier:
22204983
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 410; Journal Issue: 3; Other Information: Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ACETYLATION; BIOLOGICAL FUNCTIONS; CELL PROLIFERATION; FIBROBLASTS; INFLAMMATION; LYMPHOCYTES; LYMPHOKINES; METHYL TRANSFERASES; RHEUMATIC DISEASES