Activation of aryl hydrocarbon receptor (AhR) in mesenchymal stem cells modulates macrophage polarization in asthma
Activation of aryl hydrocarbon receptor (AhR) in mesenchymal stem cells modulates macrophage polarization in asthma
复制标题
间充质干细胞中芳烃受体（AhR）的激活调节哮喘中的巨噬细胞极化
DOI：
10.1080/1547691x.2019.1706671
复制
发表时间：
2020-01-01
影响因子：
3.3
通讯作者：
Xu, Ting
中科院分区：
文献类型：
--
作者：
Cui, Zhuang;Feng, Yuan;Xu, Ting
巨噬细胞极化已被证明在哮喘发病机制中发挥重要作用。间充质干细胞（MSC）具有调节巨噬细胞从促炎M1表型向抗炎M2表型分化的能力。然而，MSC-巨噬细胞相互作用对哮喘发展的影响以及导致这种相互作用的潜在机制在很大程度上仍然未知。本研究的目的是探讨在蟑螂提取物（CRE）诱导的哮喘小鼠模型中，MSC上表达的AhR在巨噬细胞极化中的作用。研究表明，在该模型中，MSC使巨噬细胞从促炎M1表型向抗炎M2表型极化。作为M1标志物的白细胞介素（IL）-6，IL-1 β和NOS 2的mRNA水平显著降低，而选择的M2标志物如Arg-1，FIZZ 1和YM-1的mRNA水平显著增强。还观察到，芳烃受体（AhR）信号在哮喘发病过程中显着增加，表现为AhR，CYP 1a 1和CYP 1b 1的mRNA表达增强。还观察到升高的AhR信号传导能够减弱哮喘的发作。在CRE诱导的哮喘模型中，使用AhR拮抗剂（CH 223191）导致AhR信号传导的显著抑制和M2标志物表达的增加，但导致M1标志物表达的升高。综上所述，目前的研究表明，MSC可以调节巨噬细胞极化，部分通过激活AhR信号在CRE-induced哮喘。
Macrophage polarization has been demonstrated to exert a vital role on asthma pathogenesis. Mesenchymal stem cells (MSC) have the capacity to modulate macrophage differentiation from a pro-inflammatory M1 phenotype toward an anti-inflammatory M2 phenotype. However, the impact of MSC-macrophage interactions on asthma development and underlying mechanisms responsible for this interaction remain largely unknown. The aim of this study was to investigate the role of AhR expressed on MSC in macrophage polarization in a cockroach extract (CRE)-induced asthma mouse model. The studies here revealed that MSC polarized macrophages from a pro-inflammatory M1 phenotype toward an anti-inflammatory M2 phenotype in this model. The mRNA levels of interleukin (IL)-6, IL-1 beta, and NOS2 as M1 markers were significantly decreased while those of select M2 markers such as Arg-1, FIZZ1, and YM-1 were significantly enhanced. It was also observed that aryl hydrocarbon receptor (AhR) signaling was significantly increased during asthma pathogenesis as demonstrated by enhanced mRNA expression of AhR, CYP1a1, and CYP1b1. It was also seen that the elevated AhR signaling was able to attenuate the onset of asthma. Use of an AhR antagonist (CH223191) resulted in significant inhibition of the AhR signaling and increases in M2 marker expression, but led to elevation of expression of M1 markers in the CRE-induced asthma model. Taken together, the current study showed that MSC can modulate macrophage polarization, in part, via activation of AhR signaling during CRE-induced asthma.