Lai Aaron Y, Swayze Richard D, El-Husseini Alaa, Song Cai
Department of Psychiatry, Neurochemical Research Unit, University of Alberta, Canada.
J Neuroimmunol. 2006 Jun;175(1-2):97-106. doi: 10.1016/j.jneuroim.2006.03.001. Epub 2006 Apr 19.
Interleukin (IL)-1beta is a pro-inflammatory cytokine involved in modulating inflammation and stress responses in the brain. Central administration of IL-1beta impairs both memory functions and long-term potentiation (LTP) induction. However, the molecular events responsible for the downstream effects of IL-1beta are not fully understood. Given the potential regulatory role of IL-1beta in LTP, we assessed whether IL-1beta influences surface expression and phosphorylation of glutamate receptors. We found that IL-1beta, 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-1beta 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-1beta effects on GluR1 phosphorylation and surface expression. NMDA-mediated calcium influx was also regulated by IL-1beta. These findings suggest that IL-1beta selectively regulates AMPA receptor phosphorylation and surface expression through extracellular calcium and an unknown mechanism involving NMDA receptor activity.
白细胞介素（IL）-1β是一种促炎细胞因子，参与调节大脑中的炎症和应激反应。脑室内注射IL-1β会损害记忆功能和长时程增强（LTP）诱导。然而，导致IL-1β下游效应的分子事件尚未完全明确。鉴于IL-1β在LTP中的潜在调节作用，我们评估了IL-1β是否影响谷氨酸受体的表面表达和磷酸化。我们发现，IL-1β而非IL-10或肿瘤坏死因子（TNF）-α下调了α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体亚基GluR1的表面表达和Ser831磷酸化。阻断IL-1β受体活性的药物消除了这些效应。相比之下，未观察到N-甲基-D-天冬氨酸（NMDA）受体亚基NR1的表面表达有变化。抑制NMDA受体活性或耗尽细胞外钙可阻断IL-1β对GluR1磷酸化和表面表达的影响。NMDA介导的钙内流也受IL-1β调节。这些发现表明，IL-1β通过细胞外钙和一种涉及NMDA受体活性的未知机制选择性调节AMPA受体磷酸化和表面表达。
