Matrine derivate MASM suppresses LPS-induced phenotypic and functional maturation of murine bone marrow-derived dendritic cells.
Matrine derivate MASM suppresses LPS-induced phenotypic and functional maturation of murine bone marrow-derived dendritic cells.
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DOI：
10.1016/j.intimp.2016.04.022
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发表时间：
2016-07
影响因子：
5.6
通讯作者：
Jing Xu;Yang Qi;Wei-Heng Xu;Ying Liu;Lie Qiu;Ke-Qi Wang;Honggang Hu;Zhi-gao He;Jun-Ping Zhang-Jun-Ping
中科院分区：
文献类型：
--
作者：
Jing Xu;Yang Qi;Wei-Heng Xu;Ying Liu;Lie Qiu;Ke-Qi Wang;Honggang Hu;Zhi-gao He;Jun-Ping Zhang-Jun-Ping
树突状细胞（DC）的成熟过程是T细胞免疫应答和免疫耐受形成的关键步骤。在这项研究中，我们评估了MASM，一种新的衍生物的天然化合物苦参碱，具有显着的抗炎和免疫调节性能，其有效性，以抑制脂多糖（LPS）诱导的小鼠骨髓来源的树突状细胞的成熟。在这里，我们表明，MASM深刻抑制LPS诱导的表型和功能性DC成熟。MASM以浓度依赖性方式抑制LPS诱导的共刺激分子CD 80和CD 86的表达。MASM还能抑制LPS诱导的DC释放IL-12 p70、TNF-α、IL-6和NO。MASM处理的DC通过甘露糖受体介导的内吞作用在抗原捕获方面是高效的，但对同种异体T细胞增殖的刺激能力较弱。MASM还能抑制LPS诱导的PI 3 K/Akt、MAPK和NF-κB通路。这些新的发现为MASM在影响DC中的免疫药理学作用提供了新的见解。
Dendritic cell (DC) maturation process is a crucial step for the development of T cell immune responses and immune tolerance. In this study, we evaluated MASM, a novel derivative of the natural compound matrine that possesses a significant anti-inflammatory and immune-regulating property, for its efficacy to inhibit lipopolysaccharides (LPS)-induced maturation of murine bone marrow-derived dendritic cells. Here we show that MASM profoundly suppresses LPS-induced phenotypic and functional DC maturation. MASM inhibited LPS-induced expression of costimulatory molecules CD80 and CD86 in a concentration-dependent manner. MASM also attenuated LPS-induced IL-12p70, TNF-α, IL-6 and NO release of DCs. The MASM-treated DCs were highly efficient at antigen capture via mannose receptor-mediated endocytosis but showed weak stimulatory capacity for allogeneic T cell proliferation. Furthermore, MASM inhibited LPS-induced PI3K/Akt, MAPK and NF-κB pathways. These novel findings provide new insight into the immunopharmacological role of MASM in impacting on the DCs.