A Central Nervous System-Restricted Isoform of the Interleukin-1 Receptor Accessory Protein Modulates Neuronal Responses to Interleukin-1

被引：99

作者：

Smith, Dirk E. ^{[1
]}

Lipsky, Brian P. ^{[1
]}

Russell, Chris ^{[2
]}

Ketchem, Randal R. ^{[3
]}

Kirchner, Jacqueline ^{[1
]}

Hensley, Kelly ^{[1
]}

Huang, Yangyang ^{[4
]}

Friedman, Wilma J. ^{[4
]}

Boissonneault, Vincent ^{[5
,6
]}

Plante, Marie-Michele ^{[5
,6
]}

Rivest, Serge ^{[5
,6
]}

Sims, John E. ^{[1
]}

机构：

[1] Amgen Inc, Dept Inflammat Res, Seattle, WA 98119 USA

[2] Amgen Inc, Dept Mol Sci, Seattle, WA 98119 USA

[3] Amgen Inc, Dept Prot Sci, Seattle, WA 98119 USA

[4] Rutgers State Univ, Dept Biol Sci, Newark, NJ 07102 USA

[5] CHUL Res Ctr, Mol Endocrinol Lab, Ste Foy, PQ G1V 4G2, Canada

[6] Univ Laval, Ste Foy, PQ G1V 4G2, Canada

来源：

IMMUNITY | 2009年 / 30卷 / 06期

基金：

加拿大健康研究院;

关键词：

NF-KAPPA-B; IL-1; RECEPTOR; AUTOIMMUNE ENCEPHALOMYELITIS; MENTAL-RETARDATION; NEGATIVE REGULATOR; IL1RAPL1; GENE; MAP KINASE; ACTIVATION; COMPLEX; INHIBITION;

D O I：

10.1016/j.immuni.2009.03.020

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Interleukin-1 (IL-1) has multiple functions in both the periphery and the central nervous system (CNS) and is regulated at many levels. We identified an isoform of the IL-1 receptor (IL-1R) accessory protein (termed AcPb) that is expressed exclusively in the CNS. AcPb interacted with IL-1 and the IL-1R 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 wildtype mice. These findings implicate AcPb as an additional component of the highly regulated IL-1 system and suggest that it may play a role in modulating CNS responses to IL-1 and the interplay between inflammation and neuronal survival.

引用

页码：817 / 831

页数：15

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