Expression of macrophage-derived chemokine (MDC) mRNA in macrophages is enhanced by interleukin-1β, tumor necrosis factor α, and lipopolysaccharide

A cDNA encoding the C-C chemokine MDC was isolated from a human macrophage cDNA library by differential hybridization using monocyte- and macrophage-specific cDNA probes. During monocyte to macrophage differentiation in vitro, MDC expression is first detected after 1 day of culturing and reaches maximums levels after 6, days when macrophages have fully 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 inflammatory protein-1 alpha (MIP-1 alpha), MIP-2, interleukin-1 beta (IL-1 beta), and tumor necrosis factor alpha (TNF-alpha) response much faster to LPS, Furthermore, MDC expression in macrophages is enhanced by the inflammatory mediators TNF-alpha and IL-1 beta. Similar to other TNF-alpha/IL-1 beta-inducible genes, costimulation of macrophages with both cytokines leads to higher MDC expression levels than stimulation with a single cytokine. By contrast, both resting and activated monocytes do not express MDC mRNA.