Regional Heterogeneity and Diversity in Cytokine and Chemokine Production by Astroglia: Differential Responses to HIV-1 Tat, gp120, and Morphine Revealed by Multiplex Analysis
- 2 February 2010
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Proteome Research
- Vol. 9 (4), 1795-1804
- https://doi.org/10.1021/pr900926n
Abstract
HIV-infected individuals who abuse opiates show a faster progression to AIDS and higher incidence of encephalitis. The HIV-1 proteins Tat and gp120 have been shown to cause neurodegenerative changes either in vitro or when injected or expressed in the CNS, and we have shown that opiate drugs can exacerbate neurotoxic effects in the striatum through direct actions on pharmacologically discrete subpopulations of μ-opioid receptor-expressing astroglia. Opiate coexposure also significantly enhances release of specific inflammatory mediators by astroglia from the striatum, and we theorize that astroglial reactivity may underlie aspects of HIV neuropathology. To determine whether astroglia from different regions of the central nervous system have distinct, intrinsic responses to HIV-1 proteins and opiates, we used multiplex suspension array analyses to define and compare the inflammatory signature of cytokines released by murine astrocytes grown from cerebral cortex, cerebellum, and spinal cord. Results demonstrate significant regional differences in baseline secretion patterns, and in responses to viral proteins. Of importance for the disease process, astrocytes from all regions have very limited inflammatory response to gp120 protein, as compared to Tat protein, either in the presence or absence of morphine. Overall, the chemokine/cytokine release is higher from spinal cord and cortical astroglia than from cerebellar astroglia, paralleling the relatively low incidence of HIV-related neuropathology in the cerebellum.Keywords
This publication has 83 references indexed in Scilit:
- Astrocytes and Ischemic InjuryStroke, 2009
- Morphine Exacerbates HIV-1 Tat-Induced Cytokine Production in Astrocytes through Convergent Effects on [Ca2+]i, NF-κB Trafficking and TranscriptionPLOS ONE, 2008
- Astrocytes in multiple sclerosis: A product of their environmentCellular and Molecular Life Sciences, 2008
- Cell‐specific actions of HIV‐Tat and morphine on opioid receptor expression in gliaJournal of Neuroscience Research, 2008
- Differential Distribution of Kir4.1 in Spinal Cord Astrocytes Suggests Regional Differences in K+ HomeostasisJournal of Neurophysiology, 2007
- Identification of Astrocyte-expressed Factors That Modulate Neural Stem/Progenitor Cell DifferentiationStem Cells and Development, 2006
- Distribution of two splice variants of the glutamate transporter GLT‐1 in rat brain and pituitaryGlia, 2002
- Inhibition of CXCR4-Dependent HIV-1 Infection by Extracellular HIV-1 TatBiochemical and Biophysical Research Communications, 2000
- Human Immunodeficiency Virus Type 1 Envelope Glycoprotein gp120 Induces Tumor Necrosis Factora in AstrocytesJournal of Neuro-AIDS, 1999
- Tat Protein from HIV-1 Activates MAP Kinase in Granular Neurons and Glial Cells from Rat CerebellumBiochemical and Biophysical Research Communications, 1997