Bacterial lipopolysaccharide rapidly inhibits expression of C-C chemokine receptors in human monocytes

Antonio Sica, Alessandra Saccani, Alessandro Borsatti, Christine A. Power, Timothy N C Wells, Walter Luini, Nadia Polentarutti, Silvano Sozzani, Alberto Mantovani

Research output: Contribution to journalArticlepeer-review

Abstract

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 reduction of CCR2 mRNA levels, which binds MCP-1 and -3. CCR1 and CCR5 mRNAs were also reduced, though to a lesser extent, whereas CXCR2 was unaffected. 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 expected, LPS-induced inhibition of CCR2 mRNA expression was associated with a reduction of both MCP-1 binding and chemotactic responsiveness. The capacity to inhibit CCR2 expression in monocytes was shared by other microbial agents and cytokines (inactivated Streprotocci, Propionibacterium acnes, and to a lesser extent, IL-1 and TNF- α). In contrast, IL-2 augmented CCR2 expression and MCP-1 itself had no effect. These results suggest that, regulation of receptor expression in addition to agonist production is likely a crucial point in the regulation of the chemokine system.

Original languageEnglish
Pages (from-to)969-974
Number of pages6
JournalJournal of Experimental Medicine
Volume185
Issue number5
DOIs
Publication statusPublished - 1997

ASJC Scopus subject areas

  • Immunology

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