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 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.
Sica
A
A
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Saccani
A
A
Borsatti
A
A
Power
C A
CA
Wells
T N
TN
Luini
W
W
Polentarutti
N
N
Sozzani
S
S
Mantovani
A
A
D018932:Chemokine CCL2 / Q000378:metabolism; D054410:Chemokine CCL7; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D016207:Cytokines; D015536:Down-Regulation; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D018945:Monocyte Chemoattractant Proteins / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine / Q000096:biosynthesis*; D013997:Time Factors
C515450:CCL7 protein, human; C515334:CCR2 protein, human; D018932:Chemokine CCL2; D054410:Chemokine CCL7; D016207:Cytokines; D008070:Lipopolysaccharides; D018945:Monocyte Chemoattractant Proteins; D012333:RNA, Messenger; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine