Abstract
Astrocytes respond to stimulation with the chemokine RANTES (regulated on activation, normal T cell expressed) by production of a series of cytokines and chemokines, including tumor necrosis factor-alpha (TNF-alpha) and monocyte chemoattractant protein-1 (MCP-1). In the present study we demonstrate that RANTES induces TNF, which in turn stimulates subsequent production of MCP-1. TNF-R1 (p55) serves as the principal receptor responsible for MCP-1 synthesis. The results define an astrocyte proinflammatory cascade that amplifies synthesis of proinflammatory mediators. The implications of these findings to inflammatory diseases of the central nervous system are discussed.
Copyright 2003 Wiley-Liss, Inc.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antibodies / pharmacology
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Antigens, CD / metabolism
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Astrocytes / drug effects
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Astrocytes / metabolism*
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Cells, Cultured
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Chemokine CCL2 / metabolism*
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Chemokine CCL4
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Chemokine CCL5 / physiology*
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Chemokine CXCL2
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Disease Models, Animal
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Enzyme-Linked Immunosorbent Assay
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Immunohistochemistry
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Macrophage Inflammatory Proteins / metabolism
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Mice
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Mice, Inbred BALB C
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Mice, Knockout
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Monokines / metabolism
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Nuclease Protection Assays / methods
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Protein Synthesis Inhibitors / pharmacology
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Receptors, Tumor Necrosis Factor / metabolism
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Receptors, Tumor Necrosis Factor, Type I
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Time Factors
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Tumor Necrosis Factor-alpha / immunology
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Tumor Necrosis Factor-alpha / physiology*
Substances
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Antibodies
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Antigens, CD
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Chemokine CCL2
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Chemokine CCL4
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Chemokine CCL5
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Chemokine CXCL2
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Macrophage Inflammatory Proteins
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Monokines
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Protein Synthesis Inhibitors
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Receptors, Tumor Necrosis Factor
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Receptors, Tumor Necrosis Factor, Type I
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Tumor Necrosis Factor-alpha