CD14 dictates differential activation of mesenchymal stromal cells through AKT, NF-κB and P38 signals
CD14 dictates differential activation of mesenchymal stromal cells through AKT, NF-κB and P38 signals
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CD14 通过 AKT、NF-κ B 和 P38 信号指示间充质基质细胞的差异激活
DOI：
10.1042/bsr20190807
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发表时间：
2019-07-05
影响因子：
4
通讯作者：
Piao, Jinmei
中科院分区：
文献类型：
--
作者：
Jiang, Menghui;Gao, Tianlin;Piao, Jinmei
间充质基质细胞（Mesenchymal stromal cells，MSCs）广泛存在于多种组织中，具有多向分化潜能和免疫调节功能。近年来，间充质干细胞已成为治疗各种退行性疾病和自身免疫性疾病的有前途的工具。在不同的微环境中，MSC的性质可以被改变。因此，探讨影响MSC功能的因素具有重要意义。Toll样受体（TLR）在骨髓间充质干细胞中的存在已被证明根据以前的研究。同时，我们还对小鼠和人骨髓间充质干细胞中TLRs的表达进行了研究，并显示了不同来源的骨髓间充质干细胞中TLRs的表达模式。此外，我们还探讨了TLR和TLR信号通路在MSC中的作用。有趣的是，TLR 4的激活诱导细胞因子和一些特定基因在MSC中的表达。然而，与巨噬细胞相比，MSC保留低得多的mRNA水平。我们检测了不同来源的MSCs中在TLR 4信号通路中起重要作用的CD 14的表达，发现MSCs几乎不表达CD 14。此外，在MSC中仅观察到TLR 4信号通路的部分激活，而AKT、NF-κ B和P38没有激活。在本研究中，我们定义了TLR在MSC中的表达、功能和激活，这对于设计基于MSC的疗法至关重要。
Mesenchymal stromal cells (MSCs) widely exist in many tissues and have multiple differentiation potential and immunomodulatory capacities. Recently, MSCs have become promising tools for the treatment of various degenerative disorders and autoimmune diseases. The properties of MSCs could be modified in different microenvironments. Thus, it is important to explore the factors controlling MSC function. The presence of Toll-like receptors (TLRs) in MSCs was demonstrated according to previous studies. Consistently, we also illustrated the expression of TLRs in both murine and human MSCs, and displayed that the expression patterns of TLRs in MSCs from different sources. Furthermore, we explored the role of TLR and TLR signaling pathway in MSCs. Interestingly, activation of TLR4-induced expression of cytokines and some specific genes in MSCs. However, MSCs retained much lower mRNA level compared with macrophages. We explored the expression of CD14 in MSCs from different sources, which played a vital role in TLR4 signaling pathway, and found that MSCs are almost negative for CD14. Moreover, only partial activation of TLR4 signaling pathway was observed in MSCs, with no activation of AKT, NF-kappa B and P38. Here, in the study we defined TLR expression, function and activation in MSCs, which is critical for designing MSC-based therapies.