Lipocalin-2 Acts as a Neuroinflammatogen in Lipopolysaccharide-injected Mice.
Lipocalin-2 Acts as a Neuroinflammatogen in Lipopolysaccharide-injected Mice.
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DOI：
10.5607/en.2014.23.2.155
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发表时间：
2014-06
影响因子：
2.4
通讯作者：
Suk K
中科院分区：
文献类型：
--
作者：
Jin M;Jang E;Suk K
Lipocalin-2(Lcn2)是多种细胞过程的关键调节因子。最近的研究表明，Lcn2在中枢神经系统损伤和神经系统疾病中也发挥着重要作用，如脊髓损伤、中风、实验性自身免疫性脑脊髓炎和神经退行性疾病。在这里，我们研究了Lcn2在脂多糖(LPS)诱导的神经炎症的啮齿动物模型中的作用。Lcn2主要表达于内皮细胞、星形胶质细胞和小胶质细胞。接下来，我们使用Lcn2缺陷小鼠进一步研究Lcn2在神经炎症中的作用。LCN2缺乏减弱了内毒素诱导的脑内神经胶质细胞的激活。在一项使用神经胶质细胞/神经元共培养的机制研究中，Lcn2缺乏降低了神经胶质细胞的毒性。我们的结果表明，Lcn2在脂多糖诱导的神经炎性反应中起中心作用，在过度和慢性炎症条件下，Lcn2可能参与了神经毒性神经胶质细胞的失控激活。
Lipocalin-2 (LCN2) is a key mediator of various cellular processes. Recent studies have indicated that LCN2 also plays an important role in central nervous system (CNS) injuries and neurological diseases, such as spinal cord injury, stroke, experimental autoimmune encephalomyelitis, and neurodegenerative diseases. Here, we investigated the role of LCN2 in a rodent model of lipopolysaccharide (LPS)-induced neuroinflammation. At 24 hours after intraperitoneal injection of LPS, LCN2 expression was strongly induced in the brain; LCN2 was mainly expressed in endothelial cells, astrocytes, and microglia. Next, we used LCN2-deficient mice to further investigate the role of LCN2 in neuroinflammation. LCN2 deficiency attenuated LPS-induced glial activation in the brain. In a mechanistic study employing glia/neuron co-cultures, LCN2 deficiency reduced glial neurotoxicity. Our results indicate that LCN2 plays a central role in the neuroinflammatory responses following LPS administration, and that LCN2 might contribute to the uncontrolled neurotoxic glial activation under excessive and chronic inflammatory conditions.