Distinct expressions of three cytokines by IL-1-stimulated astrocytes in vitro and in AIDS brain.
Interleukin-1 (IL-1) is elevated in brain tissue of individuals who died with acquired immunodeficiency syndrome (AIDS) and other diseases where this cytokine likely stimulates reactive astrocytosis. IL-1 stimulates, among others, production of interleukin-6 (IL-6), granulocyte macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor-alpha (TNF-alpha) in cultured astrocytes and astrocytoma cell lines. These and other cytokines may contribute to the neuropathogenesis after infection by human immunodeficiency virus type-1 (HIV-1). For example, concentration of TNF-alpha is increased in brain tissue of individuals who died with AIDS and correlates with the severity of AIDS Dementia Complex (ADC). TNF-alpha and IL-6 have been immunocytochemically detected in brain tissue but they have not been localized to astrocytes. We, therefore, examined the expression of IL-6, GM-CSF, and TNF-alpha in human primary astrocytes and astrocytoma cell lines U251 and 253 exposed to IL-1 in serum-free medium. In addition, we immunocytochemically assayed GM-CSF expression by astrocytes in brain tissue (n = 8). The three cytokines were differentially induced in cultured astrocytes by IL-1. The astrocytoma cell lines recapitulated cytokine-specific patterns of expression in astrocytes. The patterns were characterized by amounts produced, compartmentalization (intra- and/or extracellular), time courses, and optimal doses of IL-1 for induction. GM-SCF-like immunoreactivity was detected in some but not all, GFAP+ cells. GM-CSF+/GFAP+ cells were detected in only three of seven cases containing GM-CSF immunoreactivity. Thus, a discrepancy may exist between human astrocytic cytokine expression in vitro and in tissue. Novel methods therefore may need to be developed to recapitulate in vitro the heterogeneity of astrocytic cytokine expression in AIDS and other brain tissue.
Division of Neuroscience and Behavioral Science, National Institute of Mental Health, National Institutes of Health, Rockville, Maryland 20857 USA.
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Vitkovic
J J
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Chatham
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A
da Cunha
D015526:AIDS Dementia Complex / Q000378:metabolism / Q000473:pathology; D000163:Acquired Immunodeficiency Syndrome / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D016477:Artifacts; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D001254:Astrocytoma / Q000473:pathology; D001932:Brain Neoplasms / Q000473:pathology; D002478:Cells, Cultured; D005110:Extracellular Space / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D015967:Gene Expression Regulation, Viral; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis / Q000235:genetics; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics
D005904:Glial Fibrillary Acidic Protein; D007375:Interleukin-1; D015850:Interleukin-6; D009419:Nerve Tissue Proteins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor