Alcohol Regulates HIV-1-Mediated Astrocyte Inflammatory Responses Via cPLA2 Signaling Pathway

dc.creatorPandey, Richa
dc.creatorGhorpade, Anuja
dc.date.accessioned2019-08-22T19:39:00Z
dc.date.available2019-08-22T19:39:00Z
dc.date.issued2015-03
dc.date.submitted2015-02-18T07:52:28-08:00
dc.description.abstractAlcohol (EtOH) abuse and HIV-1 remain significant public health problems. Globally, drinkers have approximately 70-77% higher risk of HIV-infection than non-drinkers. The prevalence of alcohol abuse among HIV-positive individuals has been estimated to be between 29-60% in the United States. Many studies showed that neurodegeneration in alcohol abusers include exacerbated neuroinflammation and oxidative damage. However, how EtOH regulates HIV-1-induced astrocyte neuroinflammation is unknown. Thus, we explored mechanism(s) involved in alcohol-mediated activation of human astrocytes with HIV-1 and subsquent alterations in their inflammatory functions. Alcohol exposure altered the morphology of astrocytes, proinflammatory responses and induced cytotoxicity in a dose-dependent manner. Time-depended changes were also evaluated. Alcohol and HIV-1 co-treatment decreased cell viability and proliferation, while increasing apoptosis and mitochondrial depolarization. Alcohol and HIV-1 together increased the levels of proinflammatory molecules, IL-1b, TNF-a, CXCL8, TIMP-1 and more importantly, arachidonic acid, known to be downstream of cPLA2. Consistent with this observation, phospho-cPLA2 levels were augmented in HIV-1 and EtOH co-treatment as compared to HIV-1 or EtOH alone. COX2 was upregulated as measured by real time PCR and western blot, whereas co-treatment of HIV-1 and EtOH decreased CYP2E1 levels as compared to EtOH alone. In summary, our results demonstrate that EtOH-mediated astrocyte inflammation and cytotoxicity in context of HAND occurs via cPLA2 signaling.
dc.identifier.urihttps://hdl.handle.net/20.500.12503/26575
dc.language.isoen
dc.titleAlcohol Regulates HIV-1-Mediated Astrocyte Inflammatory Responses Via cPLA2 Signaling Pathway
dc.typeposter
dc.type.materialtext

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