Divergent regulation of the murine CC chemokine C10 by Th(1) and Th(2) cytokines |
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Authors: | Orlofsky A Wu Y Prystowsky M B |
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Institution: | Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA. orlofsky@aecom.yu.edu |
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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. |
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