143. Interleukin-1R3 mediates interleukin-1 induced potassium current increase through fast activation of Akt kinase

Inflammatory cytokine interleukin-1 (IL-1) performs multiple functions in the central nervous system. The type 1 IL-1 receptor (IL-1R1) and the IL-1 receptor accesory protein (IL-1RAcP) form a functional IL-1 receptor complex that is thought to mediate most, if not all, IL-1-induced effects. Several recent studies, however, suggested the existence of a heretofore unidentified receptor for IL-1. In this study, we report that the IL-1R1 gene contains an internal promoter which drives the transcription of a shortened IL-1R1 mRNA. This mRNA is the template for an novel IL-1 receptor protein that is identical with IL-1R1 at the C-terminus, but with a shorter extracellular domain at the N-terminus. We have termed this molecule IL-1R3. The mRNA and protein for IL-1R3 are expressed in normal and two strains of commercially available IL-1R1 knockout mice. In addition, immunohistochemical staining indicates that IL-1R3 is expressed exclusively in neurons, whereas IL-1R1 can be localized in non-neuronal cells of the brain. Furthermore, IL-1 binds specifically to IL-1R3 when it is complexed with the newly discovered alternative IL-1 receptor accessory protein, IL-1RAcPb. Stimulation of neurons expressing both IL-1R3 and IL-1RAcpb causes fast activation of the Akt kinase, which leads to an increase in voltage-gated potassium current. These results demonstrate IL-1R3/IL-1RAcPb complex mediates a unique subset of IL-1 activity.