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

详细信息    查看全文

• 作者：Kazunobu Shinoda ; Ken Nakagawa ; Takeo Kosaka ; Nobuyuki Tanaka ; Takahiro Maeda ; Hidaka Kono ; Ryuichi Mizuno ; Eiji Kikuchi ; Akira Miyajima ; Kazuo Umezawa ; Mototsugu Oya
• 关键词：Dendritic cells ; NF-κ ; B inhibitor ; Immunoregulation
• 刊名：Human Immunology
• 出版年：2010
• 出版时间：August 2010
• 年：2010
• 卷：71
• 期：8
• 页码：763-770
• 全文大小：1168 K

文摘

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 proinflammatory 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.