HIV-Encephalitis: Mechanisms for CXCL10 Induction in Astrocytes
Issue Date
2009-06-23Author
Williams, Rachel
Publisher
University of Kansas
Format
146 pages
Type
Dissertation
Degree Level
Ph.D.
Discipline
Molecular & Integrative Physiology
Rights
This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.
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Show full item recordAbstract
With the prevalence of HIV-associated neurocognitive disorders (HAND)
increasing, understanding the mechanisms by which HIV induces neuro-inflammation and subsequent neuronal damage is of paramount importance. We hypothesized that HIV-1 and IFN-γ/TNF-α co-operation could increase CXCL10 expression in astrocytes through redox sensitive pathways. Our initial studies focused on determining which signaling pathways were involved in CXCL10 induction in HIV-1 and cytokine treated astrocytes. The next studies were aimed at determining which HIV-1 protein was co-operating with IFN-γ and TNF-α to cause this effect. Additionally, to verify if an oxidative burst was impacting CXCL10 regulation through redox sensitive pathways we utilized apocynin, an inhibitor of NADPH oxidase. Apocynin was also able to diminish Jnk, Erk1/2, and Akt pathway activation,decrease NF-κB activation and decrease CXCL10 expression, improving neuronal survival. This data has implications for the development of therapeutic strategies aimed at reducing the release of pro-inflammatory agents to prevent HIV-1 neuropathogenesis.
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