SELECTIVE INDUCTION OF THE BETA-CHEMOKINE C10 BY IL-4 IN MOUSE MACROPHAGES

The beta chemokines are a family of 8- to 12-kDa leukocyte chemoattrac tants that are typically produced by activated macrophages or lymphocy tes. We examined the expression in primary macrophages of a recently d escribed, and as yet functionally uncharacterized, murine beta chemoki ne, C10, and contrasted its regulation with that of several other beta chemokines. Although three other beta chemokines, macrophage inflamma tory protein-1 alpha (MIP-1 alpha), JE, and RANTES, were all induced b y LPS treatment of bone marrow-derived macrophages (BMM) and/or reside nt peritoneal macrophages (RPM), LP stimulation of C10 was never obser ved. Conversely, IL-3 and granulocyte macrophage-CSF (CM-CSF) strongly induced C10 in both macrophage populations, whereas MIP-1 alpha and R ANTES showed a weaker induction restricted to BMM. JE was strongly ind uced but only in BMM. Finally, IL-4 strongly induced C10 in a dose-dep endent manner in both BMM and RPM but failed to stimulate any of the o ther three beta chemokines. The accumulation of C10 protein in culture supernatants paralleled the induction of mRNA, and the combination of IL-4 and CM-CSF led to enhanced protein levels. The expression of the C10 message in response to cytokines was completely blocked by cycloh eximide, whereas the other three chemokines were all overexpressed in the presence of this inhibitor. These results demonstrate a sharp dive rgence between the regulation of C10 expression and that of other chem okines and suggest that this molecule may have distinct functions in h ost defense.