Lipocalin-2 Is a Chemokine Inducer in the Central Nervous System ROLE OF CHEMOKINE LIGAND 10 (CXCL10) IN LIPOCALIN-2-INDUCED CELL MIGRATION
Lipocalin-2 Is a Chemokine Inducer in the Central Nervous System ROLE OF CHEMOKINE LIGAND 10 (CXCL10) IN LIPOCALIN-2-INDUCED CELL MIGRATION
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DOI：
10.1074/jbc.m111.299248
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发表时间：
2011-12-23
影响因子：
4.8
通讯作者：
Suk, Kyoungho
中科院分区：
文献类型：
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作者：
Lee, Shinrye;Kim, Jong-Heon;Suk, Kyoungho
分泌蛋白 lipocalin-2 (LCN2) 与多种细胞过程有关，包括细胞形态和迁移。然而，人们对 LCN2 在 CNS 中的作用知之甚少。在这里，我们证明 LCN2 通过上调大脑中的趋化因子来促进细胞迁移。使用培养的神经胶质细胞、微血管内皮细胞和神经元细胞的研究表明，LCN2 可能充当中枢神经系统中多种细胞类型的趋化因子诱导剂。特别是，星形胶质细胞中 JAK2/STAT3 和 IKK/NF-kappa B 通路对 CXCL10 的上调在 LCN2 诱导的细胞迁移中发挥着关键作用。使用小鼠模型在体内验证了 LCN2 在中枢神经系统中的细胞迁移促进活性。 LPS 注射或局灶性损伤后，大脑中 LCN2 的表达显着增加。缺乏 LCN2 的小鼠在神经炎症或损伤模型中表现出星形胶质细胞向损伤部位迁移受损，CXCL10 表达降低。因此，在炎症条件下分泌的 LCN2 蛋白可能会通过诱导 CNS 细胞分泌趋化因子（例如 CXCL10）来招募额外的炎症细胞，从而放大神经炎症。
The secreted protein lipocalin-2 (LCN2) has been implicated in diverse cellular processes, including cell morphology and migration. Little is known, however, about the role of LCN2 in the CNS. Here, we show that LCN2 promotes cell migration through up-regulation of chemokines in brain. Studies using cultured glial cells, microvascular endothelial cells, and neuronal cells suggest that LCN2 may act as a chemokine inducer on the multiple cell types in the CNS. In particular, up-regulation of CXCL10 by JAK2/STAT3 and IKK/NF-kappa B pathways in astrocytes played a pivotal role in LCN2-induced cell migration. The cell migration-promoting activity of LCN2 in the CNS was verified in vivo using mouse models. The expression of LCN2 was notably increased in brain following LPS injection or focal injury. Mice lacking LCN2 showed the impaired migration of astrocytes to injury sites with a reduced CXCL10 expression in the neuroinflammation or injury models. Thus, the LCN2 proteins, secreted under inflammatory conditions, may amplify neuroinflammation by inducing CNS cells to secrete chemokines such as CXCL10, which recruit additional inflammatory cells.