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-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.
PubMed ID: 20933498
PMC ID: PMC2981639
Article link: Biochem Biophys Res Commun.
Grant support: NS 041862 NINDS NIH HHS , NS48837 NINDS NIH HHS , R01 NS041862-09 NINDS NIH HHS , R01 NS063878 NINDS NIH HHS , R01 NS063878-02 NINDS NIH HHS , R01 NS063878-03 NINDS NIH HHS , R01 NS43113 NINDS NIH HHS , R01 NS041862 NINDS NIH HHS , R01 NS048837 NINDS NIH HHS
Genes referenced: cxcl8 grin2b mmp1 mmp7