Research Unit of Infection and Immunity, Department of Pathophysiology, West China College of Basic and Forensic Medicine, Sichuan University, Chengdu, 610041, China.
Comprehensive Pneumology Center (CPC), Institute of Lung Biology and Disease, Helmholtz Zentrum München, Neuherberg, Germany.
Immunol Res. 2017 Oct;65(5):1065-1073. doi: 10.1007/s12026-017-8948-5.
Growth arrest-specific gene 7 (Gas7) is preferentially expressed in terminally differentiated brain cells and plays a crucial role during neuronal development and neurite outgrowth. Apart from that, Gas7 was found to be abundantly expressed in immune cells like murine macrophage without knowing the actual roles in immune reaction. By using the Illumina microarray analysis, we observed a clear induction of Gas7 but no other Gas family members in murine M1-polarized alveolar macrophage, which was further confirmed by RT-qPCR, Western blotting, and immunostaining analysis, suggesting a likelihood that Gas7 may participate in murine alveolar macrophage polarization. Moreover, we found that the upregulation of Gas7 in M1-polarized alveolar macrophage was almost fully blocked by IKK selective inhibitor BMS, which links Gas7 induction to nuclear factor kappa beta (NF-κB) signaling activation. Interestingly, we found that Gas7 knockdown by small interfering RNA transfection did not affect the pro-inflammatory cytokine gene Tnf and Ilb expression, whereas the expressions of canonic M1 marker gene Nos2 and other M1-dependent genes Il12b, Il6, Cxcl1, Cxcl2, and Cxcl9 were found to be reduced. Furthermore, Gas7-related M1 gene expression in alveolar macrophage was not dependent on NF-κB and STAT1 pathway. Our results demonstrate that Gas7 is potentially involved in regulation of murine M1 alveolar macrophage polarization.
Gas7 was induced in LPS/IFNγ mediated M1 polarization. Gas7 are induced during time course of M1 polarization. Gas7 upregulation was dependent on NF-κB pathway in M1 polarized AMs. Gas7 knockdown reduced the M1 markers gene expression in M1 polarized AMs.
生长停滞特异性基因 7（Gas7）在终末分化的脑细胞中优先表达，在神经元发育和神经突生长中发挥关键作用。除此之外，Gas7 在免疫细胞如鼠巨噬细胞中大量表达，但在免疫反应中的实际作用尚不清楚。通过使用 Illumina 微阵列分析，我们观察到 Gas7 在鼠 M1 极化肺泡巨噬细胞中明显诱导，但其他 Gas 家族成员没有诱导，这进一步通过 RT-qPCR、Western blotting 和免疫染色分析得到证实，表明 Gas7 可能参与鼠肺泡巨噬细胞极化。此外，我们发现 M1 极化肺泡巨噬细胞中 Gas7 的上调几乎完全被 IKK 选择性抑制剂 BMS 阻断，这将 Gas7 的诱导与核因子 kappa beta（NF-κB）信号激活联系起来。有趣的是，我们发现 Gas7 通过小干扰 RNA 转染的敲低并不影响促炎细胞因子基因 Tnf 和 Ilb 的表达，而经典 M1 标记基因 Nos2 和其他 M1 依赖性基因 Il12b、Il6、Cxcl1、Cxcl2 和 Cxcl9 的表达则降低。此外，肺泡巨噬细胞中 Gas7 相关的 M1 基因表达不依赖于 NF-κB 和 STAT1 途径。我们的结果表明，Gas7 可能参与调节鼠 M1 肺泡巨噬细胞极化。
Gas7 在 LPS/IFNγ 介导的 M1 极化中被诱导。Gas7 在 M1 极化的时间过程中被诱导。M1 极化 AM 中 Gas7 的上调依赖于 NF-κB 途径。Gas7 敲低降低了 M1 极化 AM 中的 M1 标记基因表达。
