Induction of monocyte chemoattractant protein-1 in HIV-1 Tat-stimulated astrocytes and elevation in AIDS dementia.
Activated monocytes release a number of substances, including inflammatory cytokines and eicosanoids, that are highly toxic to cells of the central nervous system. Because monocytic infiltration of the central nervous system closely correlates with HIV-1-associated dementia, it has been suggested that monocyte-derived toxins mediate nervous system damage. In the present study, we show that the HIV-1 transactivator protein Tat significantly increases astrocytic expression and release of monocyte chemoattractant protein-1 (MCP-1). Astrocytic release of beta-chemokines, which are relatively less selective for monocytes, including RANTES, macrophage inflammatory protein-1alpha, and macrophage inflammatory protein-1beta, was not observed. We also show that MCP-1 is expressed in the brains of patients with HIV-1-associated dementia and that, of the beta-chemokines tested, only MCP-1 could be detected in the cerebrospinal fluid of patients with this condition. Together, these data provide a potential link between the presence of HIV-1 in the brain and the monocytic infiltration that may substantially contribute to dementia.
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Laboratory of Molecular Medicine and Neuroscience, National Institute of Neurological Disorders and Stroke, Building 36, Room 5W21, National Institutes of Health, Bethesda, MD 20892, USA. conant@codon.nih.gov
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D015526:AIDS Dementia Complex / Q000097:blood / Q000134:cerebrospinal fluid / Q000209:etiology / Q000378:metabolism*; D000328:Adult; D001253:Astrocytes / Q000187:drug effects*; D001921:Brain / Q000378:metabolism; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis* / Q000097:blood / Q000134:cerebrospinal fluid; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000032:analysis; D015696:Gene Products, tat / Q000494:pharmacology*; D015497:HIV-1; D006801:Humans; D019402:Macrophage Inflammatory Proteins / Q000032:analysis; D008875:Middle Aged; D009000:Monocytes; D011446:Prospective Studies; D054322:tat Gene Products, Human Immunodeficiency Virus
D018932:Chemokine CCL2; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D015696:Gene Products, tat; D019402:Macrophage Inflammatory Proteins; D054322:tat Gene Products, Human Immunodeficiency Virus