Growth arrest-specific protein 7 regulates the murine M1 alveolar macrophage polarization
Growth arrest-specific protein 7 regulates the murine M1 alveolar macrophage polarization
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生长停滞特异性蛋白 7 调节小鼠 M1 肺泡巨噬细胞极化
DOI：
10.1007/s12026-017-8948-5
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发表时间：
2017-09
影响因子：
4.4
通讯作者：
Huang Ning
中科院分区：
文献类型：
--
作者：
Xu Qian;Liu Xiaofan;Wang Xinyuan;Hua Yuanqi;Wang Xiaoying;Chen Junli;Li Jingyu;Wang Yi;Stoeger Tobias;Chen Shanze;Huang Ning
生长停滞特异性基因7（Gas 7）在终末分化的脑细胞中优先表达，在神经元发育和轴突生长中起着重要作用。除此之外，Gas 7被发现在免疫细胞如鼠巨噬细胞中大量表达，而不知道在免疫反应中的实际作用。通过使用Illumina微阵列分析，我们在鼠M1极化肺泡巨噬细胞中观察到Gas 7的明显诱导，但没有其他Gas家族成员，这通过RT-qPCR、Western印迹和免疫染色分析进一步证实，表明Gas 7可能参与鼠肺泡巨噬细胞极化。此外，我们发现在M1极化肺泡巨噬细胞中Gas 7的上调几乎被IKK选择性抑制剂BMS完全阻断，这将Gas 7诱导与核因子κ β（NF-κB）信号激活联系起来。有趣的是，我们发现通过小干扰RNA转染敲低Gas 7并不影响促炎细胞因子基因Tnf和Ilb的表达，而发现典型M1标记基因Nos 2和其他M1依赖性基因I112 b、I16、Cxcl 1、Cxcl 2和Cxcl 9的表达降低。肺泡巨噬细胞Gas 7相关M1基因表达不依赖于NF-κB和STAT 1通路。结果表明，Gas 7可能参与了小鼠肺泡巨噬细胞M1极化的调控; Gas 7在LPS/IFNγ介导的M1极化过程中被诱导表达;在M1极化的AM中，Gas 7的上调依赖于NF-κB通路; Gas 7的敲低可降低M1极化AM中M1标记基因的表达。
AbstractGrowth 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 murinemacrophage 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.HighlightsGas7 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.
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DOI：
10.1073/pnas.95.19.11423
发表时间：
1998-09-15
影响因子：
11.1
作者：
Ju, YT;Chang, ACY;Lin-Chao, S
通讯作者：
Lin-Chao, S
影响因子：
--
作者：
Tseng RC;Chang JW;Mao JS;Tsai CD;Wu PC;Lin CJ;Lu YL;Liao SY;Cheng HC;Hsu HS;Wang YC
通讯作者：
Wang YC
影响因子：
4.4
作者：
Gao, CJ;Guo, HT;Kuo, PC
通讯作者：
Kuo, PC
影响因子：
3
作者：
S. Sciarretta;Derek Yee;Varun Shenoy;Narayani Nagarajan;J. Sadoshima
通讯作者：
S. Sciarretta;Derek Yee;Varun Shenoy;Narayani Nagarajan;J. Sadoshima
影响因子：
6.2
作者：
Paglinawan, R;Malipiero, U;Fontana, A
通讯作者：
Fontana, A