Abstract
Fractalkine (FKN), a chemokine highly expressed in the central nervous system, participates in inflammatory responses operative in many brain disorders including HIV-1 associated dementia (HAD). In this report, HIV-1 progeny virions and pro-inflammatory products led to FKN production associated with neuronal injury and apoptosis. FKN was produced by neurons and astrocytes; but differentially produced by the two cell types. Laboratory tests paralleled those in infected people where cerebrospinal fluid FKN levels in HIV-1 infected cognitively impaired (n=16) patients were found to be increased when compared to infected patients without cognitive impairment (n=8, P=0.0345). These results demonstrate a possible role of FKN in HAD pathogenesis.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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AIDS Dementia Complex / cerebrospinal fluid
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AIDS Dementia Complex / immunology
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AIDS Dementia Complex / metabolism*
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AIDS Dementia Complex / pathology*
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Adult
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Astrocytes / drug effects
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Astrocytes / immunology
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Astrocytes / metabolism
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Astrocytes / virology
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Cells, Cultured
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Chemokine CX3CL1
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Chemokines, CX3C / biosynthesis
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Chemokines, CX3C / cerebrospinal fluid
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Chemokines, CX3C / metabolism*
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Fetus
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Glutamic Acid / toxicity
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HIV-1 / physiology
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Humans
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Membrane Proteins / biosynthesis
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Membrane Proteins / cerebrospinal fluid
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Membrane Proteins / metabolism*
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Middle Aged
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Neurons / immunology
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Neurons / metabolism*
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Neurons / pathology*
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Neurons / virology
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Recombinant Proteins / pharmacology
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Tumor Necrosis Factor-alpha / pharmacology
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Up-Regulation / immunology
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Viral Proteins / pharmacology
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Virion / physiology
Substances
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CX3CL1 protein, human
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Chemokine CX3CL1
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Chemokines, CX3C
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Membrane Proteins
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Recombinant Proteins
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Tumor Necrosis Factor-alpha
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Viral Proteins
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Glutamic Acid