Soluble factors from IL-1β-stimulated astrocytes activate NR1a/NR2B receptors: Implications for HIV-1-induced neurodegeneration

Astrocytes play an important role in astrocyte-neuron homeostasis. In HIV-1-infected brain, interleukin 1 beta (IL-1 beta) activation of astrocytes contributes to neurodegeneration. However, the molecular mechanisms underlying 1L-1 beta-activated-astrocytes-induced neurodegeneration in HIV-1-infected brain are largely unknown. We hypothesize that secretory factors from the activated astrocytes affect N-methyl-D-aspartate (NMDA) receptor, a major pathway implicated in HIV-1-associated neurodegeneration. To test this hypothesis, we studied effects of IL-1 beta-stimulated astrocyte conditioned medium (ACM+) for its ability to activate NR1a/NR2B receptors expressed on Xenopus oocytes. Astrocytes treated with IL-1 beta 20 ng/ml for 24 h induced CXCL8, CCL2, MMP1 and MMP7. Pressure ejection of the ACM(+) produced an inward current in NR1a/NR2B-expressing oocytes. The inward current produced by ACM(+) was blocked by NMDA receptor antagonist, APV but not by non-NMDA receptor antagonist, CNQX. These results suggest that IL-1 beta stimulated astrocytes activate NR1a/NR2B receptors which may have implications in HIV-1-associated neurodegeneration. (C) 2010 Elsevier Inc. All rights reserved.