Exploring New Inflammatory Biomarkers and Pathways during LPS-Induced M1 Polarization.
Exploring New Inflammatory Biomarkers and Pathways during LPS-Induced M1 Polarization.
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DOI：
10.1155/2016/6986175
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发表时间：
2016
影响因子：
4.6
通讯作者：
Brites D
中科院分区：
文献类型：
--
作者：
Cunha C;Gomes C;Vaz AR;Brites D
识别触发小胶质细胞激活的介质和将非编码microRNA(MiRNA)转移到外体是剖析神经退行性变机制的关键。我们利用脂多糖(LPS)诱导的N9小胶质细胞活化来探索新的生物标志物/信号通路，并鉴定细胞及其衍生的外切体中的炎性miRNA(炎症miR)。上调iNOS和MHC-II(M1标记物)，下调精氨酸酶1、FIZZ1(M2标记物)和CX3CR1(M0/M2极化)，证实了N9LPS处理的细胞转换为M1表型，正如巨噬细胞/小胶质细胞所描述的那样。MFG-E8上调进一步证实了细胞增殖增加，激活了TLR4/TLR2/NF-κB通路，并增强了吞噬功能。我们在这些细胞中发现了NLRP3-炎症小体的激活，这可能是我们观察到的细胞外细胞因子HMGB1和基质金属蛋白酶-9含量增加的原因。我们首次证明了M1极化的N9细胞中的炎症-miR图谱(上调的miR-155和miR-146a加上下调的miR-124)，在激活的巨噬细胞/小胶质细胞中被其他人注意到，在它们的衍生外体中被复制，可能调节受体细胞的炎症反应和传播过程。数据显示，脂多糖处理的N9细胞的行为类似于M1极化的小胶质细胞/巨噬细胞，同时为药物发现提供了新的靶点。特别是，这项研究对神经炎症过程中的外体循环miRNA产生了新的见解，这对于针对小胶质细胞激活的新兴治疗方法非常重要。
Identification of mediators triggering microglia activation and transference of noncoding microRNA (miRNA) into exosomes are critical to dissect the mechanisms underlying neurodegeneration. We used lipopolysaccharide- (LPS-) induced N9 microglia activation to explore new biomarkers/signaling pathways and to identify inflammatory miRNA (inflamma-miR) in cells and their derived exosomes. Upregulation of iNOS and MHC-II (M1-markers) and downregulation of arginase 1, FIZZ1 (M2-markers), and CX3CR1 (M0/M2 polarization) confirmed the switch of N9 LPS-treated cells into the M1 phenotype, as described for macrophages/microglia. Cells showed increased proliferation, activated TLR4/TLR2/NF-κB pathway, and enhanced phagocytosis, further corroborated by upregulated MFG-E8. We found NLRP3-inflammasome activation in these cells, probably accounting for the increased extracellular content of the cytokine HMGB1 and of the MMP-9 we have observed. We demonstrate for the first time that the inflamma-miR profiling (upregulated miR-155 and miR-146a plus downregulated miR-124) in M1 polarized N9 cells, noticed by others in activated macrophages/microglia, was replicated in their derived exosomes, likely regulating the inflammatory response of recipient cells and dissemination processes. Data show that LPS-treated N9 cells behave like M1 polarized microglia/macrophages, while providing new targets for drug discovery. In particular, the study yields novel insights into the exosomal circulating miRNA during neuroinflammation important for emerging therapeutic approaches targeting microglia activation.
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影响因子：
3.9
作者：
Cătană CS;Calin GA;Berindan-Neagoe I
通讯作者：
Berindan-Neagoe I
影响因子：
4.2
作者：
Cho, KO;La, HO;Kim, SY
通讯作者：
Kim, SY
影响因子：
6.2
作者：
Durafourt, Bryce A.;Moore, Craig S.;Antel, Jack P.
通讯作者：
Antel, Jack P.
影响因子：
5.3
作者：
Brites D;Vaz AR
通讯作者：
Vaz AR
影响因子：
5.3
作者：
Brites D;Fernandes A
通讯作者：
Fernandes A