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PMID: 9120403 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

The Journal of experimental medicine ·Vol. 185 ·No. 5 ·1997-03-03 ·Pages 969-74

Sica A, Saccani A, Borsatti A, Power CA, Wells TN, Luini W, Polentarutti N, Sozzani S, Mantovani A

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 Streptococci, Propionibacterium acnes, and to a lesser extent, IL-1 and TNF-alpha). 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.

MeSH Terms
Chemokine CCL2/metabolism Chemokine CCL7 Chemotaxis, Leukocyte/drug effects Cytokines Down-Regulation Humans Lipopolysaccharides/pharmacology Monocyte Chemoattractant Proteins/metabolism Monocytes/drug effects RNA, Messenger/metabolism Receptors, CCR2 Receptors, Chemokine Receptors, Cytokine/biosynthesis Time Factors
Chemicals
CCL7 protein, human CCR2 protein, human Chemokine CCL2 Chemokine CCL7 Cytokines Lipopolysaccharides Monocyte Chemoattractant Proteins RNA, Messenger Receptors, CCR2 Receptors, Chemokine Receptors, Cytokine
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Sica A
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Saccani A
Borsatti A
Power C A
Wells T N
Luini W
Polentarutti N
Sozzani S
Mantovani A
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.185.5.969
Published
1997-03-03
Pages
969-74
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2196159
Subset
IM
External Links
PubMed source DOI: 10.1084/jem.185.5.969 PMC Full Text View journal details
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