Neuron-specific effects of interleukin-1β are mediated by a novel isoform of the IL-1 receptor accessory protein

Yangyang Huang, Dirk E. Smith, Osvaldo Ibáñez-Sandoval, John E. Sims, Wilma J. Friedman

Research output: Contribution to journalArticlepeer-review

76 Scopus citations

Abstract

In the CNS, interleukin-11β (IL-11β) is synthesized and released during injury, infection, and disease, mediating inflammatory responses. However, IL-11β is also present in the brain under physiological conditions, and can influence hippocampal neuronal function. Several cell-specific IL-1-mediated signaling pathways and functions have been identified in neurons and astrocytes, but their mechanisms have not been fully defined. In astrocytes, IL-11β induced both the p38 MAPK and NF-κB (nuclear factor κB) pathways regulating inflammatory responses, however in hippocampal neurons IL-11β activated p38 but not NF-κB. Additionally, IL-11β induced Src phosphorylation at 0.01 ng/ml in hippocampal neurons, a dose 1000-fold lower than that used to stimulate inflammatory responses. IL-1 signaling requires the type 1 IL-1 receptor and the IL-1 receptor accessory protein (IL-1RAcP) as a receptor partner. We previously reported a novel isoform of the IL-1RAcP, IL-1RAcPb, found exclusively in CNS neurons. In this study, we demonstrate that AcPb specifically mediates IL-1β activation of p-Src and potentiation of NMDA-induced calcium influx in mouse hippocampal neurons in a dose-dependent manner. Mice lacking the AcPb, but retaining the AcP, isoform were deficient in IL-11β regulation of p-Src in neurons. AcPb also played a modulatory role in the activation of p38 MAPK, but had no effect on NF-κB signaling. The restricted expression of AcPb in CNS neurons, therefore, governs specific neuronal signaling and functional responses to IL-11β.

Original languageEnglish (US)
Pages (from-to)18048-18059
Number of pages12
JournalJournal of Neuroscience
Volume31
Issue number49
DOIs
StatePublished - Dec 7 2011

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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