A Biodegradable Mg-Based Alloy Inhibited the Inflammatory Response of THP-1 Cell-Derived Macrophages Through the TRPM7-PI3K-AKT1 Signaling Axis
A Biodegradable Mg-Based Alloy Inhibited the Inflammatory Response of THP-1 Cell-Derived Macrophages Through the TRPM7-PI3K-AKT1 Signaling Axis
复制标题
可生物降解的镁基合金通过 TRPM7-PI3K-AKT1 信号轴抑制 THP-1 细胞来源的巨噬细胞的炎症反应
DOI：
10.3389/fimmu.2019.02798
复制
发表时间：
2019-12-03
影响因子：
7.3
通讯作者：
Chen, Tongxin
中科院分区：
文献类型：
--
作者：
Jin, Liang;Chen, Chenxin;Chen, Tongxin
镁基合金具有良好的力学性能、生物可降解性、生物相容性，尤其是良好的抗炎性能，是临床应用的理想生物材料。然而，镁基合金抑制炎症的确切信号传导机制尚未阐明。在这里，我们研究了Mg-2.1Nd-0.2Zn-0.5Zr合金（记作JDBM）对脂多糖（LPS）诱导的巨噬细胞的影响。THP-1细胞衍生的巨噬细胞在JDBM、Ti−6Al−4V合金（Ti）、15% JDBM浸提液和7.5 mM MgCl 2上培养1 h，然后加入LPS指定时间;实验包括阴性和阳性对照。结果表明，加味DBM、提取物和MgCl 2均能降低LPS诱导的肿瘤坏死因子（TNF）和白细胞介素（IL）-6的表达。然而，在Ti或JDBM上的巨噬细胞没有形态学变化。与阳性对照组相比，提取物和MgCl 2下调了toll样受体（TLR）-4和MYD 88的表达，并通过灭活IKK-α/β、IKβ-α、P65、P38和JNK的磷酸化来抑制LPS诱导的核因子-κ B（NF-κB B）和丝裂原活化蛋白激酶（MAPK）信号通路。此外，LPS诱导的活性氧（ROS）的表达也减少提取物和MgCl 2。有趣的是，LPS诱导的TNF和IL-6的表达可以通过敲低巨噬细胞的TRPM 7来恢复，在提取物或MgCl 2的存在下。机械上，AKT和AKT 1的活性通过提取物或MgCl 2与LPS增加，并被PI 3 K抑制剂阻断，而siRNA TRPM 7仅抑制AKT 1。总之，我们的结果证明了镁基合金的降解产物，特别是镁，并通过激活TRPM 7-PI 3 K-AKT 1信号通路解决炎症，这可能是促进可生物降解镁基合金应用的潜在优势或目标。
Mg-based alloys might be ideal biomaterials in clinical applications owing to favorable mechanical properties, biodegradability, biocompatibility, and especially their anti-inflammatory properties. However, the precise signaling mechanism underlying the inhibition of inflammation by Mg-based alloys has not been elucidated. Here, we investigated the effects of a Mg-2.1Nd-0.2Zn-0.5Zr alloy (denoted as JDBM) on lipopolysaccharide (LPS)-induced macrophages. THP-1 cell-derived macrophages were cultured on JDBM, Ti−6Al−4V alloy (Ti), 15% extract of JDBM, and 7.5 mM of MgCl2 for 1 h before the addition of LPS for an indicated time; the experiments included negative and positive controls. Our results showed JDBM, extract, and MgCl2 could decrease LPS-induced tumor necrosis factor (TNF) and interleukin (IL)-6 expression. However, there were no morphologic changes in macrophages on Ti or JDBM. Mechanically, extract and MgCl2 downregulated the expression of toll-like receptor (TLR)-4 and MYD88 compared with the positive control and inhibited LPS-induced nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways by inactivation of the phosphorylation of IKK-α/β, IKβ-α, P65, P38, and JNK. Additionally, the LPS-induced reactive oxygen species (ROS) expression was also decreased by extract and MgCl2. Interestingly, the expression of LPS-induced TNF and IL-6 could be recovered by knocking down TRPM7 of macrophages, in the presence of extract or MgCl2. Mechanically, the activities of AKT and AKT1 were increased by extract or MgCl2 with LPS and were blocked by a PI3K inhibitor, whereas siRNA TRPM7 inhibited only AKT1. Together, our results demonstrated the degradation products of Mg-based alloy, especially magnesium, and resolved inflammation by activation of the TRPM7–PI3K–AKT1 signaling pathway, which may be a potential advantage or target to promote biodegradable Mg-based alloy applications.