The regulatory role of ProBDNF in monocyte function: Implications in Stanford type-A aortic dissection disease
The regulatory role of ProBDNF in monocyte function: Implications in Stanford type-A aortic dissection disease
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ProBDNF 在单核细胞功能中的调节作用：对斯坦福 A 型主动脉夹层疾病的影响
DOI：
10.1096/fj.201901905rr
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发表时间：
2019-12-22
期刊：
影响因子：
4.8
通讯作者：
Dai, Ru-Ping
中科院分区：
文献类型：
--
作者：
Shen, Wei-Yun;Luo, Cong;Dai, Ru-Ping
据报道，脑源性神经营养因子前体（proBDNF）在动物实验中可增强单核/巨噬细胞的功能障碍。然而，在人类炎症性疾病中，proBDNF在单核细胞功能障碍中的作用尚不清楚。在本研究中，我们发现在脂多糖处理后，来自健康供体（HD）的单核细胞中proBDNF和泛神经营养受体p75显著上调。外源性proBDNF处理上调CD40和单核细胞中促炎细胞因子的表达，包括白细胞介素(IL)-1 β、IL-6和肿瘤坏死因子(TNF)- α。在Stanford a型急性主动脉夹层（AAD）患者中，proBDNF在CD14(+)CD163(+)CX3CR1(+) M2-中表达上调，而在CD14(+)CD68(+)CCR2(+) m1样单核细胞中表达上调。此外，AAD患者的血清激活了HD培养的PBMCs中促炎细胞因子的基因表达，而proBDNF单克隆抗体（Ab-proB）治疗可减弱这种基因表达。这些发现表明，m2样单核细胞中proBDNF的上调可能有助于AAD的促炎反应。
Brain-derived neurotrophic factor precursor (proBDNF) has been reported to strengthen the dysfunction of monocytes/macrophages in animal studies. However, it is still unknown the roles of proBDNF in the dysfunction of monocytes in the inflammatory diseases in humans. In the present study, we showed that proBDNF and pan neurotrophic receptor p75 were significantly upregulated in monocytes from healthy donors (HD) after lipopolysaccharide treatment. Exogenous proBDNF treatment upregulated CD40 and proinflammatory cytokines expression in monocytes including interleukin (IL)-1 beta, IL-6, and tumor necrosis factor (TNF)-alpha. In Stanford type-A acute aortic dissection (AAD) patients, proBDNF was upregulated in CD14(+)CD163(+)CX3CR1(+) M2- but not CD14(+)CD68(+)CCR2(+)M1-like monocytes. In addition, sera from AAD patients activated gene expression of proinflammatory cytokines in cultured PBMCs from HD, which was attenuated by proBDNF monoclonal antibody (Ab-proB) treatment. These findings suggested that upregulation of proBDNF in M2-like monocytes may contribute to the proinflammatory response in the AAD.