IL-1? Correlates With HIV-1 Tat-induced EAAT-2 Expression Decrease

Human immunodeficiency virus(HIV)infection frequently results in neurological damage,such as a HIV-associated neurocognitive disorders(HAND).Our previous study prompts that decreased excitatory amino acid transporter 2(EAAT-2)on the astrocytes accompanied with high levels of glutamate in the synaptic cleft is a key factor responsible for neuronal damage in the process of HAND.However,the underlying molecular mechanism remains unclear.In this study,we report the decreased EAAT-2 in the frontal cortex of SIV-infected macaques.Moreover,decreased EAAT-2 correlated with the apoptosis and presence of SIV-1 Tat using double-label immunohistochemical staining.IL-1? was overexpressed in the frontal cortex of SIV-infected macaques.Statistical analysis showed that IL-1? was significantly increased,and negatively correlated with EAAT-2 expression.Furthermore,western blot study using primary C57 astrocytes showed that HIV-1 Tat can down-regulate EAAT-2 expression.IL-1? was associated with decreased levels of EAAT-2 induced by HIV-1 Tat,which could be prevented by B122(antibodies against IL-1?).In conclusion,these results indicate that IL-1? may be involved in HIV-1 Tat-induced decrease EAAT-2 expression,and subsequent neuronal apoptosis.However,the precise mechanism needs to be further explored..