dc.contributor.advisor | Buch, Shilpa J. | |
dc.contributor.author | Williams, Rachel | |
dc.date.accessioned | 2009-11-02T19:49:39Z | |
dc.date.available | 2009-11-02T19:49:39Z | |
dc.date.issued | 2009-06-23 | |
dc.date.submitted | 2009 | |
dc.identifier.other | http://dissertations.umi.com/ku:10414 | |
dc.identifier.uri | http://hdl.handle.net/1808/5577 | |
dc.description.abstract | 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. | |
dc.format.extent | 146 pages | |
dc.language.iso | EN | |
dc.publisher | University of Kansas | |
dc.rights | This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author. | |
dc.subject | Biology | |
dc.subject | Neurosciences | |
dc.subject | Molecular biology | |
dc.subject | Microbiology | |
dc.subject | Astrocytes | |
dc.subject | Cxcl10 | |
dc.subject | Hiv | |
dc.subject | Hiv-associated dementia | |
dc.subject | Ifn-gamma | |
dc.subject | Tnf-alpha | |
dc.title | HIV-Encephalitis: Mechanisms for CXCL10 Induction in Astrocytes | |
dc.type | Dissertation | |
dc.contributor.cmtemember | Gonzalez, Norberto C. | |
dc.contributor.cmtemember | Kim, Kee Jun | |
dc.contributor.cmtemember | Newell, Kathy | |
dc.contributor.cmtemember | Yankee, Thomas | |
dc.thesis.degreeDiscipline | Molecular & Integrative Physiology | |
dc.thesis.degreeLevel | Ph.D. | |
kusw.oastatus | na | |
kusw.oapolicy | This item does not meet KU Open Access policy criteria. | |
kusw.bibid | 7078943 | |
dc.rights.accessrights | openAccess | |