title: Divergent regulation of the murine CC chemokine C10 by Th(1) and Th(2) cytokines.
abstract: Chemokines are typically found as products of acute stimulation of host defence cells. In contrast, the mouse CC chemokine C10 was previously shown to be a delayed, stably induced product of macrophages treated with interleukin 3 (IL-3), IL-4 or GM-CSF. We investigated the possibility that C10 is differentially regulated by cytokines associated with Th(1)and Th(2)cells. Northern blot analysis of bone marrow-derived macrophages showed that, in addition to IL-4, the Th(2)-specific cytokines IL-10 and IL-13 upregulated C10 over a 48-h period in a dose-dependent manner. In contrast, MIP-1alpha and MCP-1/JE were induced by IL-3 or GM-CSF at 48 h and this induction was inhibited by IL-4. Interferon gamma, a Th(1)-specific product, abolished the induction of C10 mRNA and protein by either IL-3 or granulocyte-macrophage colony-stimulating factor (GM-CSF) in either bone marrow-derived or peritoneal macrophages. The inhibition of C10 production by interferon gamma was not NO dependent. Finally the GM-CSF-mediated induction of C10 in peritoneal macrophages was eliminated when these cells presented antigen to established T cells of Th(1)phenotype. The findings are consistent with a potential role for C10 in the modulation of immune reactions of Th(2)type.
authors.affiliation: Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA. orlofsky@aecom.yu.edu
authors.forename: A
authors.initials: A
authors.lastname: Orlofsky
authors.forename: Y
authors.initials: Y
authors.lastname: Wu
authors.forename: M B
authors.initials: MB
authors.lastname: Prystowsky
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000378:metabolism; D018925:Chemokines / Q000096:biosynthesis* / Q000235:genetics; D019742:Chemokines, CC / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation; D007371:Interferon-gamma / Q000502:physiology; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008808:Mice, Inbred CBA; D018417:Th1 Cells / Q000378:metabolism*; D018418:Th2 Cells / Q000378:metabolism*
chemical_list: D018925:Chemokines; D019742:Chemokines, CC; D016207:Cytokines; C070959:Ccl6 protein, mouse; D007371:Interferon-gamma