A central nervous system-restricted isoform of the interleukin-1 receptor accessory protein modulates neuronal responses to interleukin-1.
A central nervous system-restricted isoform of the interleukin-1 receptor accessory protein modulates neuronal responses to interleukin-1.
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DOI：
10.1016/j.immuni.2009.03.020
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发表时间：
2009-06-19
期刊：
影响因子：
32.4
通讯作者：
Sims, John E.
中科院分区：
文献类型：
--
作者：
Smith, Dirk E.;Lipsky, Brian P.;Russell, Chris;Ketchem, Randal R.;Kirchner, Jacqueline;Hensley, Kelly;Huang, Yangyang;Friedman, Wilma J.;Boissonneault, Vincent;Plante, Marie-Michele;Rivest, Serge;Sims, John E.
IL-1在外周和中枢神经系统(CNS)中具有多种功能，并在多个水平上进行调节。我们发现了一种新的IL-1R辅助蛋白亚型(称为AcPb)，该蛋白仅在中枢神经系统中表达。Acpb可与IL-1和IL-1受体相互作用，但不能介导典型的IL-1反应。然而，AcPb的表达在体外调节了神经元基因的表达，以响应IL-1的处理。缺乏AcPb的动物表现出完整的外周IL-1反应，并发展为实验性自身免疫性脑脊髓炎(EAE)，类似于野生型小鼠。相反，与ACP缺乏或野生型小鼠相比，AcPb缺乏的小鼠更容易受到中枢神经系统局部炎症的攻击，并遭受增强的神经元变性。这些发现表明，AcPb是高度调控的IL-1系统的一个额外成分，并表明它可能在调节中枢神经系统对IL-1的反应以及炎症和神经元存活之间的相互作用中发挥作用。
IL-1 has multiple functions in both the periphery and the central nervous system (CNS) and is regulated at many levels. We identified a novel isoform of the IL-1R Accessory Protein (termed AcPb) that is expressed exclusively in the CNS. AcPb interacted with IL-1 and the IL-1 receptor but was unable to mediate canonical IL-1 responses. AcPb expression, however, modulated neuronal gene expression in response to IL-1 treatment in vitro. Animals lacking AcPb demonstrated an intact peripheral IL-1 response and developed experimental autoimmune encephalomyelitis (EAE) similarly to wild type mice. AcPb-deficient mice were instead more vulnerable to local inflammatory challenge in the CNS and suffered enhanced neuronal degeneration as compared to AcP-deficient or wild type mice. These findings implicate AcPb as an additional component of the highly regulated IL-1 system and suggest it may play a role in modulating CNS responses to IL-1 and the interplay between inflammation and neuronal survival.
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影响因子：
4.8
作者：
Khan, JA;Brint, EK;Tong, L
通讯作者：
Tong, L
影响因子：
4.8
作者：
Li, CS;Zienkiewicz, J;Hawiger, J
通讯作者：
Hawiger, J
DOI：
10.1073/pnas.0510802103
发表时间：
2006-02-21
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
15.3
作者：
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通讯作者：
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影响因子：
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作者：
Andre, R;Lerouet, D;Rothwell, NJ
通讯作者：
Rothwell, NJ