The Gateway Reflex, which is mediated by the inflammation amplifier, directs pathogenic immune cells into the CNS.
The Gateway Reflex, which is mediated by the inflammation amplifier, directs pathogenic immune cells into the CNS.
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由炎症放大器介导的网关反射将致病性免疫细胞引导至中枢神经系统。
DOI：
10.1093/jb/mvu057
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发表时间：
2014
影响因子：
2.7
通讯作者：
M.
中科院分区：
文献类型：
--
作者：
Sabharwal;L.;Kamimura;D.;Meng;J.;Bando;H.;Ogura;H.;Nakayama;C.;Jiang;J. J.;Kumai;N.;Suzuki;H.;Atsumi;T.;Arima;Y. & Murakami;M.
脑血屏障（BBB）严格限制免疫细胞迁移到中枢神经系统（CNS），避免在正常状态下发生不必要的炎症。然而，当CNS内发生炎症时，免疫细胞可以穿过BBB，这表明可能存在创建绕过BBB的网关的特定信号。我们揭示了炎症放大器作为这种信号的机制，并确定第五腰椎（L5）脊髓的背侧血管作为网关。炎症放大器由非免疫细胞中NF-κ B和STAT的同时激活驱动，导致大量炎性趋化因子的产生以打开L5血管的通道。发现放大器的激活可以通过神经激活来调节，并且可以通过电脉冲人工操作，然后建立新的网关，网关反射，至少在小鼠中。此外，炎症放大器所需的基因已被鉴定，并且与CNS中的各种炎性疾病和病症高度相关。因此，炎症放大器的物理和/或药理学操作具有控制神经炎症的治疗价值。
The brain–blood barrier (BBB) tightly limits immune cell migration into the central nervous system (CNS), avoiding unwanted inflammation under the normal state. However, immune cells can traverse the BBB when inflammation occurs within the CNS, suggesting a certain signal that creates a gateway that bypasses the BBB might exist. We revealed the inflammation amplifier as a mechanism of this signal, and identified dorsal vessels of the fifth lumber (L5) spinal cord as the gateway. The inflammation amplifier is driven by a simultaneous activation of NF-κB and STATs in non-immune cells, causing the production of a large amount of inflammatory chemokines to open the gateway at L5 vessels. It was found that the activation of the amplifier can be modulated by neural activation and artificially operated by electric pulses followed by establishment of new gateways, Gateway Reflex, at least in mice. Furthermore, genes required for the inflammation amplifier have been identified and are highly associated with various inflammatory diseases and disorders in the CNS. Thus, physical and/or pharmacological manipulation of the inflammation amplifier holds therapeutic value to control neuro-inflammation.