A central nervous system-restricted isoform of the interleukin-1 receptor accessory protein modulates neuronal responses to interleukin-1.
Immunity, 2009/6/19;30(6):817-31.
Smith DE[1], Lipsky BP, Russell C, Ketchem RR, Kirchner J, Hensley K, Huang Y, Friedman WJ, Boissonneault V, Plante MM, Rivest S, Sims JE
Affiliations
PMID: 19481478DOI: 10.1016/j.immuni.2009.03.020
Impact factor: 43.474
Abstract
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 wild-type 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.
MeSH terms
Alternative Splicing; Amino Acid Sequence; Animals; Astrocytes; Base Sequence; Brain; Cell Line, Tumor; Cells, Cultured; Central Nervous System; Cytokines; Humans; Inflammation; Interleukin-1; Interleukin-1 Receptor Accessory Protein; Mice; Mice, Knockout; Molecular Sequence Data; Neurons; Protein Isoforms; Signal Transduction
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