Tumor necrosis factor is required for RANTES-induced astrocyte monocyte chemoattractant protein-1 production.
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.
Luo
Yi
Y
Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Berman
Michael A
MA
Abromson-Leeman
Sara R
SR
Dorf
Martin E
ME
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D015703:Antigens, CD / Q000378:metabolism; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism*; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000502:physiology*; D054426:Chemokine CXCL2; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D015846:Monokines / Q000378:metabolism; D023282:Nuclease Protection Assays / Q000379:methods; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000502:physiology*
D000906:Antibodies; D015703:Antigens, CD; D018932:Chemokine CCL2; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D054426:Chemokine CXCL2; D019402:Macrophage Inflammatory Proteins; D015846:Monokines; D011500:Protein Synthesis Inhibitors; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha