BACTERIAL LIPOPOLYSACCHARIDE RAPIDLY INHIBITS EXPRESSION OF C-C CHEMOKINE RECEPTORS IN HUMAN MONOCYTES

The present study was designed to investigate the effect of bacterial lipopolysaccharide (LPS) on C-C chemokine receptors (CCR) expressed in human mononuclear phagocytes. LPS caused a rapid and drastic reductio n of CCR2 mRNA levels, which binds MCP-1 and -3. CCR1 and CCR5 mRNAs w ere also reduced, though to a lesser extent, whereas CXCR2 was unaffec ted. The rate of nuclear transcription of CCR2 was not affected by LPS , whereas the mRNA half life was reduced from 1.5 h to 45 min. As expe cted, LPS-induced inhibition of CCR2 mRNA expression was associated wi th a reduction of both MCP-1 binding and chemotactic responsiveness. T he capacity to inhibit CCR2 expression in monocytes was shared by othe r microbial agents and cytokines (inactivated Streptococci, Propioniba cterium acnes, and to a lesser extent, IL-1 and TNF-alpha). In contras t, IL-2 augmented CCR2 expression and MCP-1 itself had no effect. Thes e results suggest that, regulation of receptor expression in addition to agonist production is likely a crucial point in the regulation of t he chemokine system.