Regulation of human dendritic cells by a novel specific nuclear factor-κB inhibitor, dehydroxymethylepoxyquinomicin

Kazunobu Shinoda, Ken Nakagawa, Takeo Kosaka, Nobuyuki Tanaka, Takahiro Maeda, Hidaka Kono, Ryuichi Mizuno, Eiji Kikuchi, Akira Miyajima, Kazuo Umezawa, Mototsugu Oya

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Regulation of antigen-presenting cells (APC) is crucial in controlling allograft rejection. Dendritic cells (DC) are the most potent APC and must mature to present antigens to T-cell receptors. During DC maturation, nuclear factor-κB (NF-κB) is a key transcriptional factor. We synthesized dehydroxymethylepoxyquinomicin (DHMEQ), which specifically inhibits the final step of nuclear translocation of activated NF-κB proteins and examined its immunoregulatory effects on human monocyte-derived DC (Mo-DC). Regulatory Mo-DC were generated by pretreatment with DHMEQ before LPS stimulation, which were termed dl-DC. DHMEQ pretreatment (5 μg/ml) completely inhibited nuclear translocation of activated NF-κB. DHMEQ significantly inhibited DC production of κproinflammatory cytokines (IL-6, TNF-α, and IL-12 p70) in a dose-dependent manner. IL-12 was most potently inhibited. However, IL-10 production by dl-DC was only moderately affected by DHMEQ. Although CD40 and the expression of HLA-DR (HLA-DR) expression on dl-DC was downregulated, CD80 and CD86 expression was moderately upregulated. Induction of T helper 1 cell responses was efficiently impaired by dl-DC. This confirmed that DHMEQ-treated Mo-DC exhibited immunoregulatory effects. These findings suggest that DHMEQ has potential as an immunosuppressive drug for human immune cells.

Original languageEnglish
Pages (from-to)763-770
Number of pages8
JournalHuman Immunology
Volume71
Issue number8
DOIs
Publication statusPublished - 2010 Aug 1

Keywords

  • Dendritic cells
  • Immunoregulation
  • NF-κB inhibitor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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