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

Tao Jing, Li Wu, Kathleen Borgmann, Sankar Surendran, Anuja Ghorpade, Jianuo Liu, Huangui Xiong

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

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 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-1β stimulated astrocytes activate NR1a/NR2B receptors which may have implications in HIV-1-associated neurodegeneration.

Original languageEnglish
Pages (from-to)241-246
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume402
Issue number2
DOIs
StatePublished - 12 Nov 2010

Keywords

  • Astrocyte
  • HIV-1
  • IL-1β
  • NMDA receptor
  • Voltage clamp
  • Xenopus oocyte

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