Secreted protein lipocalin-2 promotes microglial M1 polarization
Secreted protein lipocalin-2 promotes microglial M1 polarization
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DOI：
10.1096/fj.12-222257
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发表时间：
2013-03-01
期刊：
影响因子：
4.8
通讯作者：
Suk, Kyoungho
中科院分区：
文献类型：
--
作者：
Jang, Eunha;Lee, Shinrye;Suk, Kyoungho
活化的巨噬细胞分为两种不同的形式：经典活化（M1）或交替活化（M2）巨噬细胞。M1/M2表型极化也被认为存在于小胶质细胞。在这里，我们报道了分泌的蛋白脂载蛋白2 （LCN2）放大了激活的小胶质细胞的M1极化。LCN2蛋白（EC50 1 μ g/ml），而不是谷胱甘肽s转移酶作为对照，在培养的小鼠小胶质细胞8-24 h后增加了m1相关基因的表达。LCN2在m1极化的小胶质细胞中分泌，而在m2极化的小胶质细胞中没有分泌。LCN2抑制il -4刺激的小胶质细胞中STAT6的磷酸化，提示LCN2抑制典型的M2信号传导。在脂多糖（LPS）诱导的小鼠神经炎症模型中，LCN2在小胶质细胞中的表达明显增加。来源于lcn2缺失小鼠的原代小胶质细胞培养显示M1反应被抑制，M2反应增强。LCN2缺失小鼠注射LPS后，小胶质细胞中m1相关基因表达明显降低，这与组织学分析结果一致。通过旋转杆性能测试、疲劳测试、野外测试和物体识别任务确定，lcn2缺陷小鼠的运动行为和认知功能的神经炎症相关损伤也有所减轻。这些发现表明LCN2是脑小胶质细胞中的m1放大器。-Jang， E., Lee， S., Kim, j.h。， Kim, j - h。徐，j.w。李，w - h。， Mori， K, Nakao， K, Suk， K.分泌蛋白脂钙素-2促进小胶质细胞M1极化。中国生物医学工程学报，2013,33(2):481 - 481。www.fasebj.org
Activated macrophages are classified into two different forms: classically activated (M1) or alternatively activated (M2) macrophages. The presence of M1/M2 phenotypic polarization has also been suggested for microglia. Here, we report that the secreted protein lipocalin 2 (LCN2) amplifies M1 polarization of activated microglia. LCN2 protein (EC50 1 mu g/ml), but not glutathione S-transferase used as a control, increased the M1-related gene expression in cultured mouse microglial cells after 8-24 h. LCN2 was secreted from M1-polarized, but not M2-polarized, microglia. LCN2 inhibited phosphorylation of STAT6 in IL-4-stimulated microglia, suggesting LCN2 suppression of the canonical M2 signaling. In the lipopolysaccharide (LPS)-induced mouse neuroinflammation model, the expression of LCN2 was notably increased in microglia. Primary microglial cultures derived from LCN2-deficient mice showed a suppressed M1 response and enhanced M2 response. Mice lacking LCN2 showed a markedly reduced M1-related gene expression in microglia after LPS injection, which was consistent with the results of histological analysis. Neuroinflammation-associated impairment in motor behavior and cognitive function was also attenuated in the LCN2-deficient mice, as determined by the rotarod performance test, fatigue test, open-field test, and object recognition task. These findings suggest that LCN2 is an M1-amplifier in brain microglial cells.-Jang, E., Lee, S., Kim, J.-H., Kim, J.-H., Seo, J.-W., Lee, W.-H., Mori, K., Nakao, K., Suk, K. Secreted protein lipocalin-2 promotes microglial M1 polarization. FASEB J. 27, 1176-1190 (2013). www.fasebj.org