DHMEQ, a novel nuclear factor-κB inhibitor, induces selective depletion of alloreactive or phytohaemagglutinin-stimulated peripheral blood mononuclear cells, decreases production of T helper type 1 cytokines, and blocks maturation of dendritic cells
DHMEQ, a novel nuclear factor-κB inhibitor, induces selective depletion of alloreactive or phytohaemagglutinin-stimulated peripheral blood mononuclear cells, decreases production of T helper type 1 cytokines, and blocks maturation of dendritic cells
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DOI：
10.1111/j.1365-2567.2007.02755.x
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发表时间：
2008-06-01
期刊：
影响因子：
6.4
通讯作者：
Yokoyama, Akihito
中科院分区：
文献类型：
--
作者：
Nishioka, Chie;Ikezoe, Takayuki;Yokoyama, Akihito
脱羟甲基氧奎诺米星(DHMEQ)是一种新型的核因子-kappa B(NF-kappa B)抑制剂，已被证明对多种类型的实体瘤和血液系统的恶性细胞具有活性。本研究探讨了DHMEQ的体外抗炎作用。用3-(4，5-二甲基噻唑-2-基)-2，5-二苯基四氮唑(MTT)法检测DHMEQ对植物血凝素(PHA)刺激或同种异体反应的外周血单核细胞(PBMC)在混合淋巴细胞培养中的增殖抑制作用。相反，DHMEQ不影响静息状态下PBMC的活性。此外，实时定量聚合酶链式反应显示，DHMEQ降低了PHA刺激的PBMC和Jurkat T淋巴母细胞白血病细胞中辅助性T细胞1型(Th1)细胞因子的表达，包括白细胞介素2、干扰素-γ和肿瘤坏死因子α，并降低了细胞核中p65亚型的核因子-kappa B的水平。此外，我们还发现DHMEQ抑制树突状细胞(DC)的内吞能力，并下调细胞表面抗原CD40的表达，这表明DHMEQ既抑制了DC的成熟，也抑制了DC的功能。综上所述，这些结果提示DHMEQ可能用于治疗炎症性疾病，包括异基因造血干细胞移植后的移植物抗宿主病。
Dehydroxymethylepoxyquinomicin (DHMEQ), a novel nuclear factor kappa B (NF-kappa B) inhibitor, has been shown to be active against variety types of solid tumours as well as haematological malignant cells. This study explored the anti-inflammatory effects of DHMEQ in vitro. DHMEQ inhibited the proliferation of phytohaemagglutinin (PHA)-stimulated or alloreactive peripheral blood mononuclear cells (PBMC) in mixed lymphocyte cultures as measured using a 3-(4,5-dimethylithiazol-2-yl)-2,5-diphenyl tetrazolium (MTT) assay. In contrast, DHMEQ did not affect the viability of resting PBMC. In addition, real-time polymerase chain reaction showed that DHMEQ decreased PHA-stimulated expression of T helper type 1 (Th1) cytokines, including interleukin-2, interferon-gamma, and tumour necrosis factor alpha, in PBMC as well as Jurkat T-lymphoblastic leukaemia cells, and also decreased levels of p65 isoforms of NF-kappa B in the nucleus. Furthermore, we found that DHMEQ inhibited the endocytic capacity of dendritic cells (DCs) and down-regulated the expression of cell surface antigen CD40, suggesting that DHMEQ blocked the maturation as well as the function of DCs. Taken together, the results suggest that DHMEQ may be useful for treatment of inflammatory diseases, including graft-versus-host disease after allogenic haematopoietic stem cell transplantation.