Microglial Kv1.3 Channels and P2Y12 Receptors Differentially Regulate Cytokine and Chemokine Release from Brain Slices of Young Adult and Aged Mice.
Microglial Kv1.3 Channels and P2Y12 Receptors Differentially Regulate Cytokine and Chemokine Release from Brain Slices of Young Adult and Aged Mice.
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DOI：
10.1371/journal.pone.0128463
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Eder C
中科院分区：
文献类型：
--
作者：
Charolidi N;Schilling T;Eder C
脑卒中或创伤性脑损伤后的脑组织损伤伴随着神经炎症过程，而小胶质细胞通过产生促炎物质，包括细胞因子和趋化因子，在引起和调节神经炎症中起着核心作用。在这里，我们使用来自年轻成年和老年小鼠的脑切片，建立了原位脑损伤模型，研究细胞因子和趋化因子的产生，特别关注小胶质细胞的作用。切片制备24小时后，老年小鼠脑切片释放的促炎细胞因子TNF-α、IL-6和趋化因子CCL2、CXCL1浓度高于青年小鼠。然而，用LPS刺激最大的小胶质细胞24小时并没有显示出细胞因子和趋化因子释放量的年龄依赖性差异。小胶质细胞因子和趋化因子产生的机制在年轻成年小鼠和老年小鼠中似乎是相似的。马加藤毒素抑制小胶质细胞Kv1.3通道可降低IL-6的释放，但不影响CCL2和CXCL1的释放。相反，用PSB0739阻断小胶质细胞P2Y12受体可抑制CCL2和CXCL1的释放，而IL-6的释放不受影响。细胞因子和趋化因子的产生不会因Kir2.1 K+通道或腺苷受体的抑制剂而减少。总之，我们的数据表明，脑组织损伤诱导的细胞因子和趋化因子的产生是年龄依赖性的，并受小胶质细胞Kv1.3通道和P2Y12受体的差异调节。
Brain tissue damage following stroke or traumatic brain injury is accompanied by neuroinflammatory processes, while microglia play a central role in causing and regulating neuroinflammation via production of proinflammatory substances, including cytokines and chemokines. Here, we used brain slices, an established in situ brain injury model, from young adult and aged mice to investigate cytokine and chemokine production with particular focus on the role of microglia. Twenty four hours after slice preparation, higher concentrations of proinflammatory cytokines, i.e. TNF-α and IL-6, and chemokines, i.e. CCL2 and CXCL1, were released from brain slices of aged mice than from slices of young adult mice. However, maximal microglial stimulation with LPS for 24 h did not reveal age-dependent differences in the amounts of released cytokines and chemokines. Mechanisms underlying microglial cytokine and chemokine production appear to be similar in young adult and aged mice. Inhibition of microglial Kv1.3 channels with margatoxin reduced release of IL-6, but not release of CCL2 and CXCL1. In contrast, blockade of microglial P2Y12 receptors with PSB0739 inhibited release of CCL2 and CXCL1, whereas release of IL-6 remained unaffected. Cytokine and chemokine production was not reduced by inhibitors of Kir2.1 K+ channels or adenosine receptors. In summary, our data suggest that brain tissue damage-induced production of cytokines and chemokines is age-dependent, and differentially regulated by microglial Kv1.3 channels and P2Y12 receptors.
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影响因子：
4.1
作者：
Chen Y;Won SJ;Xu Y;Swanson RA
通讯作者：
Swanson RA
小胶质启动和对衰老中的继发性损伤的反应性增强，创伤性中枢神经系统损伤和神经退行性疾病。
影响因子：
4.7
作者：
Norden DM;Muccigrosso MM;Godbout JP
通讯作者：
Godbout JP
影响因子：
4.4
作者：
Kim, Beomsue;Jeong, Hey-kyeong;Joe, Eun-hye
通讯作者：
Joe, Eun-hye
影响因子：
5.8
作者：
Mosher, Kira Irving;Wyss-Coray, Tony
通讯作者：
Wyss-Coray, Tony
影响因子：
4.2
作者：
Njie EG;Boelen E;Stassen FR;Steinbusch HW;Borchelt DR;Streit WJ
通讯作者：
Streit WJ