Divergent regulation of the murine CC chemokine C10 by Th-1 and Th-2 cytokines

Chemokines are typically found as products of acute stimulation of host def ence cells, In contrast, the mouse CC chemokine C10 was previously shown to be a delayed, stably induced product of macrophages treated with interleuk in 3 (IL-3), IL-4 or GM-CSF. We investigated the possibility that C10 is di fferentially regulated by cytokines associated with Th-1 and Th-2 cells, No rthern blot analysis of bone marrow-derived macrophages showed that, in add ition 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-1 alpha and MCP-1/JE were induced by IL-3 or GM-CSF at 48 h and this induction was inh ibited by IL-4, Interferon gamma, a Th-1-specific product, abolished the in duction of C10 mRNA and protein by either IL-3 or granulocyte-macrophage co lony-stimulating factor (GM-CSF) in either bone marrow-derived or peritonea l macrophages, The inhibition of C10 production by interferon gamma was not NO dependent. Finally the CM-CSF-mediated induction of C10 in peritoneal m acrophages was eliminated when these cells presented antigen to established T cells of Th-1 phenotype, The findings are consistent with a potential ro le for C10 in the modulation of immune reactions of Th-2 type. (C) 2000 Aca demic Press.