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Biochem Biophys Res Commun
2010 Nov 12;4022:241-6. doi: 10.1016/j.bbrc.2010.10.006.
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Soluble factors from IL-1β-stimulated astrocytes activate NR1a/NR2B receptors: implications for HIV-1-induced neurodegeneration.
Jing T
,
Wu L
,
Borgmann K
,
Surendran S
,
Ghorpade A
,
Liu J
,
Xiong H
.
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Astrocytes play an important role in astrocyte-neuron homeostasis. In HIV-1-infected brain, interleukin 1 beta (IL-1β) activation of astrocytes contributes to neurodegeneration. However, the molecular mechanisms underlying IL-1β-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-1β-stimulated astrocyte conditioned medium (ACM+) for its ability to activate NR1a/NR2B receptors expressed on Xenopus oocytes. Astrocytes treated with IL-1β 20ng/ml for 24h 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-1β stimulated astrocytes activate NR1a/NR2B receptors which may have implications in HIV-1-associated neurodegeneration.
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