EXPRESSION OF MACROPHAGE-DERIVED-CHEMOKINE (MDC) MESSENGER-RNA IN MACROPHAGES IS ENHANCED BY INTERLEUKIN-1-BETA, TUMOR-NECROSIS-FACTOR-ALPHA, AND LIPOPOLYSACCHARIDE

A cDNA encoding the C-C chemokine MDC was isolated from a human macrop hage cDNA library by differential hybridization using monocyte- and ma crophage-specific cDNA probes. During monocyte to macrophage different iation in vitro, MDC expression is first detected after 1 day of cultu ring and reaches maximums levels after 6, days when macrophages have f ully matured, as judged from the expression of known macrophage marker genes. Exposure of macrophages to lipopolysaccharide (LPS) results in a dose-dependent increase in MDC mRNA levels, with maximum induction occurring after 6-8 h, whereas expression levels of macrophages inflam matory protein-1 alpha (MIP-1 alpha), MIP-2, interleukin-1 beta (IL-1 beta), and tumor necrosis factor alpha (TNF-alpha) response much faste r to LPS, Furthermore, MDC expression in macrophages is enhanced by th e inflammatory mediators TNF-alpha and IL-1 beta. Similar to other TNF -alpha/IL-1 beta-inducible genes, costimulation of macrophages with bo th cytokines leads to higher MDC expression levels than stimulation wi th a single cytokine. By contrast, both resting and activated monocyte s do not express MDC mRNA.