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

Sica A, Saccani A, Borsatti A, Power CA, Wells TN, Luini W, Polentarutti N, Sozzani S, Mantovani A - J. Exp. Med. (1997)

Bottom Line: As expected, LPS-induced inhibition of CCR2 mRNA expression was associated with a reduction of both MCP-1 binding and chemotactic responsiveness.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.

View Article: PubMed Central - PubMed

Affiliation: Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.

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.

Show MeSH

Related in: MedlinePlus

Inhibition by LPS of  MCP-1 binding and chemotaxis.  (A) Binding. fresh human monocytes were incubated for 1–5 h  in the presence or absence of 100  ng/ml of LPS before [125I]MCP-1  binding assay. Results are expressed as percent of bound on  total counts. (B) Chemotaxis.  Fresh human monocytes were  stimulated with 100 ng/ml of  LPS and chemotactic response to  MCP-1 (100 ng/ml) was measured after different periods as  indicated.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2196159&req=5

Figure 3: Inhibition by LPS of MCP-1 binding and chemotaxis. (A) Binding. fresh human monocytes were incubated for 1–5 h in the presence or absence of 100 ng/ml of LPS before [125I]MCP-1 binding assay. Results are expressed as percent of bound on total counts. (B) Chemotaxis. Fresh human monocytes were stimulated with 100 ng/ml of LPS and chemotactic response to MCP-1 (100 ng/ml) was measured after different periods as indicated.

Mentions: MCP-1 is a high-affinity ligand for the CCR2 receptor (23). Therefore we measured the [125I]MCP-1 binding in untreated and LPS-treated fresh human monocytes. As shown in Fig. 3 A, a significant time-dependent inhibition of the [125I]MCP-1 binding was observed after LPS treatment, which resulted in 60% of reduction after 5 h. Likewise, LPS treatment induced a strong decrease in the number of monocytes migrating in response to MCP-1 (Fig. 3 B). Thus, in human monocytes the LPS-mediated inhibition of CCR2 expression results in a marked reduction of both binding and migratory response to MCP-1, with the latter being much more sensitive to the action of LPS. A stronger inhibition of chemotaxis compared to receptor binding was previously described also for IL-8 (27).


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

Sica A, Saccani A, Borsatti A, Power CA, Wells TN, Luini W, Polentarutti N, Sozzani S, Mantovani A - J. Exp. Med. (1997)

Inhibition by LPS of  MCP-1 binding and chemotaxis.  (A) Binding. fresh human monocytes were incubated for 1–5 h  in the presence or absence of 100  ng/ml of LPS before [125I]MCP-1  binding assay. Results are expressed as percent of bound on  total counts. (B) Chemotaxis.  Fresh human monocytes were  stimulated with 100 ng/ml of  LPS and chemotactic response to  MCP-1 (100 ng/ml) was measured after different periods as  indicated.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2196159&req=5

Figure 3: Inhibition by LPS of MCP-1 binding and chemotaxis. (A) Binding. fresh human monocytes were incubated for 1–5 h in the presence or absence of 100 ng/ml of LPS before [125I]MCP-1 binding assay. Results are expressed as percent of bound on total counts. (B) Chemotaxis. Fresh human monocytes were stimulated with 100 ng/ml of LPS and chemotactic response to MCP-1 (100 ng/ml) was measured after different periods as indicated.
Mentions: MCP-1 is a high-affinity ligand for the CCR2 receptor (23). Therefore we measured the [125I]MCP-1 binding in untreated and LPS-treated fresh human monocytes. As shown in Fig. 3 A, a significant time-dependent inhibition of the [125I]MCP-1 binding was observed after LPS treatment, which resulted in 60% of reduction after 5 h. Likewise, LPS treatment induced a strong decrease in the number of monocytes migrating in response to MCP-1 (Fig. 3 B). Thus, in human monocytes the LPS-mediated inhibition of CCR2 expression results in a marked reduction of both binding and migratory response to MCP-1, with the latter being much more sensitive to the action of LPS. A stronger inhibition of chemotaxis compared to receptor binding was previously described also for IL-8 (27).

Bottom Line: As expected, LPS-induced inhibition of CCR2 mRNA expression was associated with a reduction of both MCP-1 binding and chemotactic responsiveness.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.

View Article: PubMed Central - PubMed

Affiliation: Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.

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.

Show MeSH
Related in: MedlinePlus