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孙静, 刘漪沦, 李灿等. hADMSCs影响TLR4-TRIF信号通路诱导小鼠小胶质细胞表型极化的实验研究[J]. 四川大学学报(医学版), 2019, 50(2): 164-170.
引用本文: 孙静, 刘漪沦, 李灿等. hADMSCs影响TLR4-TRIF信号通路诱导小鼠小胶质细胞表型极化的实验研究[J]. 四川大学学报(医学版), 2019, 50(2): 164-170.
SUN Jing, LIU Yi-lun, LI Can.et al. Effect of Human Adipose Mesenchymal Stem Cells on Phenotype Polarization of Mice Microglia via TLR3/TRIF Signal Pathway[J]. Journal of Sichuan University (Medical Sciences), 2019, 50(2): 164-170.
Citation: SUN Jing, LIU Yi-lun, LI Can.et al. Effect of Human Adipose Mesenchymal Stem Cells on Phenotype Polarization of Mice Microglia via TLR3/TRIF Signal Pathway[J]. Journal of Sichuan University (Medical Sciences), 2019, 50(2): 164-170.

hADMSCs影响TLR4-TRIF信号通路诱导小鼠小胶质细胞表型极化的实验研究

Effect of Human Adipose Mesenchymal Stem Cells on Phenotype Polarization of Mice Microglia via TLR3/TRIF Signal Pathway

  • 摘要: 目的研究人脂肪间充质干细胞(human adipose-derived mesenchymal stem cells,hADMSCs)对小胶质细胞表型极化的影响及机制。方法取 C57/BL6小鼠BV-2小胶质细胞,以 hADMSCs+脂多糖(LPS)间接共培养,或以单纯LPS 培养。倒置显微镜下观察细胞形态。CCK-8法检测小胶质细胞增殖能力,实时荧光定量PCR(RT-qPCR)检测小胶质细胞M1/M2表型标记物的影响,Western blot检测小胶质细胞Toll样受体4(TLR4)-β干扰素TIR结构域衔接蛋白(TRIF)信号通路相关蛋白的表达。结果与单纯LPS培养相比,hADMSCs 加入后,小胶质细胞镜下形态相似,细胞增殖活性被抑制(P<0.05),M1表型标记物的基因表达减少(P<0.05),M2表型标记物的基因表达增加(P<0.05),TRIF、TLR4、干扰素调节因子3 (IRF3)和磷酸化IRF3 (P-IRF3)蛋白的表达水平降低(P<0.05)。结论hADMSCs可抑制脂多糖(LPS)诱导的BV2小胶质细胞M1促炎表型的极化,从而诱导其向保护型M2表型极化,此作用可能与其对TLR4-TRIF信号通路活化的抑制有关。

     

    Abstract: ObjectiveTo explore the effect and mechanism of human adipose-derived mesenchymal stem cells (hADMSCs) on phenotypic polarization of microglia. MethodsBV-2 microglia of C57/BL6 mice were co-cultured with hADMSCs+lipopolysaccharide (LPS),or cultured with LPS alone. Cell morphology was observed under an inverted microscope. The effect of hADMSCs on microglial proliferation was evaluated by CCK-8 assay. The impact of hADMSCs on microglia M1/M2 phenotype markers were detected using quantitative real-time PCR (RT-qPCR). The affect of hADMSCs on the proteins expression levels of Toll-like receptor 4 (TLR4)-TIR domain containing adaptor protein inducing interferon β (TRIF) signaling pathway in BV-2 microglia was detected by using Western blot analysis. ResultsAs compared with the LPS treatment,hADMSCs treatment had no obvious effect on microglia morphology,whereas showed significant inhibition on microglial proliferation activity (P<0.05). Simultaneously,hADMSCs treatment reduced expression of microglia M1 phenotype markers (P<0.05),and increased microglia M1 phenotype markers in gene levels (P<0.05). At the same time,protein expression levels of TRIF,TLR4,phosphorylated interferon regulatory factor 3 (P-IRF3) and interferon regulatory factor 3 (IRF3) in BV-2 microglia were decreased after hADMSCs treatment. ConclusionhADMSCs can blockade the LPS-induced pro-inflammatory microglia M1 phenotype,whereas induces protective microglial M2 phenotype,which may be related to inhibition of the TLR4-TRIF signaling pathway.

     

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