| First Author | Huang Y | Year | 2011 |
| Journal | J Neurosci | Volume | 31 |
| Issue | 49 | Pages | 18048-59 |
| PubMed ID | 22159118 | Mgi Jnum | J:298383 |
| Mgi Id | MGI:6480254 | Doi | 10.1523/JNEUROSCI.4067-11.2011 |
| Citation | Huang Y, et al. (2011) Neuron-specific effects of interleukin-1beta are mediated by a novel isoform of the IL-1 receptor accessory protein. J Neurosci 31(49):18048-59 |
| abstractText | In the CNS, interleukin-1beta (IL-1beta) is synthesized and released during injury, infection, and disease, mediating inflammatory responses. However, IL-1beta 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-1beta induced both the p38 MAPK and NF-kappaB (nuclear factor kappaB) pathways regulating inflammatory responses, however in hippocampal neurons IL-1beta activated p38 but not NF-kappaB. Additionally, IL-1beta 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-1beta 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-1beta regulation of p-Src in neurons. AcPb also played a modulatory role in the activation of p38 MAPK, but had no effect on NF-kappaB signaling. The restricted expression of AcPb in CNS neurons, therefore, governs specific neuronal signaling and functional responses to IL-1beta. |
