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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.

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Related in: MedlinePlus

Effects of microbial products (A) and cytokines (C) on  CCR2 mRNA expression. B and D show the ethidium bromide stained  ribosomal RNA of A and C, respectively. Total RNA was purified from  fresh human monocytes incubated for 4 h as indicated. (A) lane 1, untreated; lane 2, LPS 100 ng/ml; lane 3, inactivated Streptococci OK432  (0.015 KE/ml); lane 4, P. acnes (10 μg/ml); lane 5, C. albicans (100 μg/ ml); lane 6, Glucan (100 μg/ml). (C) lane 1, untreated; lane 2, IL-2 (1,000  U/ml); lane 3, LPS (100 ng/ml); lane 4, TNF-α (500 U/ml); lane 5, IL-1-β  (20 ng/ml).
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Figure 4: Effects of microbial products (A) and cytokines (C) on CCR2 mRNA expression. B and D show the ethidium bromide stained ribosomal RNA of A and C, respectively. Total RNA was purified from fresh human monocytes incubated for 4 h as indicated. (A) lane 1, untreated; lane 2, LPS 100 ng/ml; lane 3, inactivated Streptococci OK432 (0.015 KE/ml); lane 4, P. acnes (10 μg/ml); lane 5, C. albicans (100 μg/ ml); lane 6, Glucan (100 μg/ml). (C) lane 1, untreated; lane 2, IL-2 (1,000 U/ml); lane 3, LPS (100 ng/ml); lane 4, TNF-α (500 U/ml); lane 5, IL-1-β (20 ng/ml).

Mentions: Having established that LPS rapidly inhibits CCR2 expression, we wanted to investigate whether other microbial agents or components and cytokines affected this chemokine receptor. We tested agents (e.g., inactivated Streptococci, Propionibacterium acnes, Candida albicans, glucan) known to affect various functions of monocytes, including chemokine production (36, 37). As shown in Fig. 4 A, CCR2 gene expression was completely suppressed either by treatment with inactivated Streptococci or P. acnes. Furthermore, the CCR2 mRNA level was also partially affected by Glucan, but not by C. albicans. Among cytokines (Fig. 4 C), we found that IL-2 stimulates CCR2 expression thus extending to monocytes recent results with T lymphocytes and NK cells (23, 28, 35). In contrast, TNF-α and IL-1β reduced CCR2 expression and MCP-1 itself had no effect (not shown).


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)

Effects of microbial products (A) and cytokines (C) on  CCR2 mRNA expression. B and D show the ethidium bromide stained  ribosomal RNA of A and C, respectively. Total RNA was purified from  fresh human monocytes incubated for 4 h as indicated. (A) lane 1, untreated; lane 2, LPS 100 ng/ml; lane 3, inactivated Streptococci OK432  (0.015 KE/ml); lane 4, P. acnes (10 μg/ml); lane 5, C. albicans (100 μg/ ml); lane 6, Glucan (100 μg/ml). (C) lane 1, untreated; lane 2, IL-2 (1,000  U/ml); lane 3, LPS (100 ng/ml); lane 4, TNF-α (500 U/ml); lane 5, IL-1-β  (20 ng/ml).
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Related In: Results  -  Collection

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

Figure 4: Effects of microbial products (A) and cytokines (C) on CCR2 mRNA expression. B and D show the ethidium bromide stained ribosomal RNA of A and C, respectively. Total RNA was purified from fresh human monocytes incubated for 4 h as indicated. (A) lane 1, untreated; lane 2, LPS 100 ng/ml; lane 3, inactivated Streptococci OK432 (0.015 KE/ml); lane 4, P. acnes (10 μg/ml); lane 5, C. albicans (100 μg/ ml); lane 6, Glucan (100 μg/ml). (C) lane 1, untreated; lane 2, IL-2 (1,000 U/ml); lane 3, LPS (100 ng/ml); lane 4, TNF-α (500 U/ml); lane 5, IL-1-β (20 ng/ml).
Mentions: Having established that LPS rapidly inhibits CCR2 expression, we wanted to investigate whether other microbial agents or components and cytokines affected this chemokine receptor. We tested agents (e.g., inactivated Streptococci, Propionibacterium acnes, Candida albicans, glucan) known to affect various functions of monocytes, including chemokine production (36, 37). As shown in Fig. 4 A, CCR2 gene expression was completely suppressed either by treatment with inactivated Streptococci or P. acnes. Furthermore, the CCR2 mRNA level was also partially affected by Glucan, but not by C. albicans. Among cytokines (Fig. 4 C), we found that IL-2 stimulates CCR2 expression thus extending to monocytes recent results with T lymphocytes and NK cells (23, 28, 35). In contrast, TNF-α and IL-1β reduced CCR2 expression and MCP-1 itself had no effect (not shown).

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