科研之友
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摘要
With the increasing prevalence of HIV-associated neurocognititve disorders (HAND), Understanding the mechanisms by which HIV-1 induces neuro-inflammation subsequent neuronal damage is important The hallmark features of HIV-encephalitis, the pathological correlate of HIV-associated Dementia (HAD), are gliosis, oxidative stress, chemokine dysregulation, and neuronal damage/death Since neuron are not infected by HIV-1, the current thinking is that these cells are damaged indirectly by pro-inflammatory chemokines released by activated glial cells CXCL10 is a neurotoxic chemokine that IS upregulated in astroglia activated by HIV-1. Tat, IFN-gamma, and TNF-alpha. In this study we have demonstrated that. HIV-1 Tat increases CXCL10 expression in IFN-gamma and TNF-alpha stimulated astrocytes via NADPH oxidase. We have shown that the treatment of astrocytes with a mixture of Tat and cytokines leads to a respiratory burst that is abrogated by apocynin, an NADPH oxidase inhibitor Pretreatment of Tat, IFN-gamma, and TNF-alpha stimulated astrocytes with apocynin also resulted in concomitant inhibition of CXCL10 expression Additionally apocynin was also able to reduce Tat and cytokine-mediated activation of the corresponding signaling molecules Erk1/2, Jnk, and Akt with a decrease in activation and nuclear translocation of NF-kappa B, important regulators of CXCL10 Induction Understanding the mechanisms involved in reducing both oxidative stress and the release of pro-inflammatory agent's could lead to the development of therapeutics aimed at decreasing neuro-inflammation In patients suffering from HAD.
- 出版日期2010-4-1
