Primary human monocytes differentiate into M2 macrophages and involve Notch-1 pathway
Primary human monocytes differentiate into M2 macrophages and involve Notch-1 pathway
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DOI：
10.1139/cjpp-2016-0319
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发表时间：
2017-03-01
影响因子：
2.1
通讯作者：
Singla, Reetu
中科院分区：
文献类型：
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作者：
Singla, Dinender K.;Wang, Jing;Singla, Reetu
本研究旨在探讨抑制原代人单核细胞中Notch-1信号通路是否能促进M2巨噬细胞分化。我们建立了一个原代人类单核细胞培养模型，以了解Notch-1信号通路的作用。单核细胞用Notch-1抑制剂DAPT或siRNA处理。我们的数据显示，在原代培养的人单核细胞中，iNOS标记的M1巨噬细胞数量显著增加。其次，促炎细胞因子IL-6和MCP-1以及肿瘤坏死因子-α在ACM中的水平升高(p<；0.05)。此外，经DAPT或siRNA治疗后，M1巨噬细胞和促炎细胞因子减少。相比之下，M2巨噬细胞显著增加，CD206和精氨酸酶-1阳性细胞在DAPT或siRNA处理组明显增加(p<；0.05)。此外，与对照组相比，相关的抗炎细胞因子IL-10和IL-1RA也显著增加(p<；0.05)。我们的结论是，用DAPT或siRNA阻断Notch-1通路可以减少人单核细胞中的促炎细胞因子，增强M2巨噬细胞的分化，增加抗炎细胞因子。因此，抑制Notch-1通路对炎症性疾病具有潜在的治疗应用前景。
The current study investigates whether inhibiting the Notch-1 signaling pathway in primary human monocytes enhances M2 macrophage differentiation. We generated a primary human monocyte cell culture model to understand the effect of the Notch-1 signaling pathway. Monocytes were treated with Notch-1 inhibitors DAPT or siRNA. Our data show that there was a significant increase in the M1 macrophage population demonstrated by iNOS marker in the primary human monocytes treated with apoptotic-conditioned medium (ACM). Next, the levels of pro-inflammatory cytokines IL-6 and MCP-1, as well as TNF-alpha, increased in ACM media (p < 0.05). Furthermore, M1 macrophages and pro-inflammatory cytokines were reduced following DAPT or siRNA treatment. Comparatively, there was a significant increase in M2 macrophages, as demonstrated by an increase in CD206 and arginase-1 positive cells treated with DAPT or siRNA (p < 0.05). Furthermore, a significant increase in the associated anti-inflammatory cytokines IL-10 and IL-1RA was also observed with respect to control groups (p < 0.05). We conclude that blocking the Notch-1 pathway with DAPT or siRNA attenuates pro-inflammatory cytokines, enhances M2 macrophage differentiation, and increases anti-inflammatory cytokines in primary human monocytes. As a result, Notch-1 pathway inhibition has potential therapeutic applications of inflammatory disease.