Interleukin‐1β upregulates functional expression of neurokinin‐1 receptor (NK‐1R) via NF‐κB in astrocytes

Publisher Website
Google Scholar
Abstract
Cytokines and neuropeptides are modulators of neuroimmunoregulation in the central nervous system (CNS). The interaction of these modulators may have important implications in CNS diseases. We investigated whether interleukin‐1β (IL‐1β) modulates the expression of neurokinin‐1 receptor (NK‐1R), the primary receptor for substance P (SP), a potent neuropeptide in the CNS. IL‐1β upregulated NK‐1R expression in human astroglioma cells (U87 MG) and primary rat astrocytes at both mRNA and protein levels. IL‐1β treatment of U87 MG cells and primary rat astrocytes led to an increase in cytosolic Ca2+ in response to SP stimulation, indicating that IL‐1β‐induced NK‐1R is functional. CP‐96,345, a specific non‐peptide NK‐1R antagonist, inhibited SP‐induced rise of [Ca2+]i in the astroglioma cells. Investigation of the mechanism responsible for IL‐1β action revealed that IL‐1β has the ability of activating nuclear factor‐κb (NF‐κB). Caffeic acid phenethyl ester (CAPE), a specific inhibitor of NF‐κB activation, not only abrogated IL‐1β‐induced NF‐κB promoter activation, but also blocked IL‐1β‐mediated induction of NK‐1R gene expression. These findings provide additional evidence that there is a biological interaction between IL‐1β and the neuropeptide SP in the CNS, which may have important implications in the inflammatory diseases in the CNS.