Interleukin-1 beta modulates AMPA receptor expression and phosphorylation in hippocampal neurons

Interleukin (IL)-1 beta is a pro-inflammatory cytokine involved in modulating inflammation and stress responses in the brain. Central administration of IL-1 beta impairs both memory functions and long-term potentiation (LTP) induction. However, the molecular events responsible for the downstream effects of IL-1 beta are not fully understood. Given the potential regulatory role of IL-1 beta in LTP, we assessed whether IL-1 beta influences surface expression and phosphorylation of glutamate receptors. We found that IL-1 beta but not IL-10 or tumour necrosis factor (TNF)-alpha, down-regulated the surface expression and Ser831 phosphorylation of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit GluR1. Agents that block IL-1 beta receptor activity abolished these effects. In contrast, no change in the surface expression of the N-methyl-D-aspartate (NMDA) receptor subunit NR1 was observed. The inhibition of NMDA receptor activity or depletion of extracellular calcium blocked IL-1 beta effects on GluR1 phosphorylation and surface expression. NMDA-mediated calcium influx was also regulated by IL-1 beta. These findings suggest that IL-1 beta selectively regulates AMPA receptor phosphorylation and surface expression through extracellular calcium and an unknown mechanism involving NMDA receptor activity. (c) 2006 Elsevier b.v. All rights reserved.