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

Interleukin (IL)-1β is a pro-inflammatory cytokine involved in modulating inflammation and stress responses in the brain. Central administration of IL-1β impairs both memory functions and long-term potentiation (LTP) induction. However, the molecular events responsible for the downstream effects of IL-1β are not fully understood. Given the potential regulatory role of IL-1β in LTP, we assessed whether IL-1β influences surface expression and phosphorylation of glutamate receptors. We found that IL-1β, but not IL-10 or tumour necrosis factor (TNF)-α, down-regulated the surface expression and Ser831 phosphorylation of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit GluR1. Agents that block IL-1β 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-1β effects on GluR1 phosphorylation and surface expression. NMDA-mediated calcium influx was also regulated by IL-1β. These findings suggest that IL-1β selectively regulates AMPA receptor phosphorylation and surface expression through extracellular calcium and an unknown mechanism involving NMDA receptor activity.