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

作者：Seong Ah Reum; Yoo Jung Yoon; Choi KyungChul; Lee Mee Hee; Lee Yoo Hyun; Lee Jeongmin; Jun Woojin; Kim Sunoh; Yoon Ho Geun^*

来源：Biochemical and Biophysical Research Communications, 2011, 410(3): 581-586.

DOI：10.1016/j.bbrc.2011.06.029

• Dephinidin
• Histone acetyltransferase inhibitor
• Inflammation
• NF-kappa B
• Cytokines
• Rheumatoid arthritis

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 this compound may be useful in preventing inflammatory arthritis.

• 出版日期2011-7-8