Ciprofloxacin inhibits advanced glycation end products-induced adhesion molecule expression on human monocytes

S. Mori, H. K. Takahashi, K. Liu, Hidenori Wake, J. Zhang, R. Liu, Tadashi Yoshino, Masahiro Nishibori

Research output: Contribution to journalArticle

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Abstract

Background and Purpose Advanced glycation end products (AGEs) subtypes, proteins or lipids that become glycated after exposure to sugars, can induce complications in diabetes. Among the various AGE subtypes, glyceraldehyde- derived AGE (AGE-2) and glycolaldehyde-derived AGE (AGE-3) are involved in inflammation in diabetic patients; monocytes are activated by these AGEs. Ciprofloxacin (CIP), a fluorinated 4-quinolone, is often used clinically to treat infections associated with diabetis due to its antibacterial properties. It also modulates immune responses in human peripheral blood mononuclear cells (PBMC) therefore we investigated the involvement of AGEs in these effects. Experimental Approach Expression of intercellular adhesion molecule (ICAM)-1, B7.1, B7.2 and CD40 was examined by flow cytometry. The production of tumour necrosis factor (TNF)-α, interferon (IFN)-γ, prostaglandin E 2 (PGE 2) and cAMP were determined by enzyme-linked immunosorbent assay. Cyclooxygenase (COX)-2 expression was determined by Western blot analysis. Lymphocyte proliferation was determined by [ 3H]- thymidine uptake. Key Results CIP induced PGE 2 production in monocytes, irrespective of the presence of AGE-2 and AGE-3, by enhancing COX-2 expression; this led to an elevation of intracellular cAMP in monocytes. Non-selective and selective COX-2 inhibitors, indomethacin and NS398, inhibited CIP-induced PGE 2 and cAMP production. In addition, CIP inhibited AGE-2- and AGE-3-induced expressions of ICAM-1, B7.1, B7.2 and CD40 in monocytes, the production of TNF-α and IFN-γ and lymphocyte proliferation in PBMC. Indomethacin, NS398 and a protein kinase A inhibitor, H89, inhibited the actions of CIP. Conclusions and Implications CIP exerts immunomodulatory activity via PGE 2, implying therapeutic potential of CIP for the treatment of AGE-2- and AGE-3-induced inflammatory responses.

Original languageEnglish
Pages (from-to)229-240
Number of pages12
JournalBritish Journal of Pharmacology
Volume161
Issue number1
DOIs
Publication statusPublished - Sep 2010

Fingerprint

Advanced Glycosylation End Products
Ciprofloxacin
Monocytes
Prostaglandins E
Intercellular Adhesion Molecule-1
Cyclooxygenase 2
Indomethacin
Interferons
Blood Cells
Tumor Necrosis Factor-alpha
4-Quinolones
Lymphocytes
Glyceraldehyde
Cyclooxygenase 2 Inhibitors
Diabetes Complications
Protein Kinase Inhibitors
Cyclic AMP-Dependent Protein Kinases
Thymidine
Flow Cytometry
Western Blotting

Keywords

  • adhesion molecule
  • advanced glycation end products
  • ciprofloxacin
  • cyclic adenosine monophosphate
  • cyclooxygenase-2
  • human
  • monocytes
  • peripheral blood mononuclear cells
  • prostaglandins E2
  • protein kinase A

ASJC Scopus subject areas

  • Pharmacology

Cite this

Ciprofloxacin inhibits advanced glycation end products-induced adhesion molecule expression on human monocytes. / Mori, S.; Takahashi, H. K.; Liu, K.; Wake, Hidenori; Zhang, J.; Liu, R.; Yoshino, Tadashi; Nishibori, Masahiro.

In: British Journal of Pharmacology, Vol. 161, No. 1, 09.2010, p. 229-240.

Research output: Contribution to journalArticle

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abstract = "Background and Purpose Advanced glycation end products (AGEs) subtypes, proteins or lipids that become glycated after exposure to sugars, can induce complications in diabetes. Among the various AGE subtypes, glyceraldehyde- derived AGE (AGE-2) and glycolaldehyde-derived AGE (AGE-3) are involved in inflammation in diabetic patients; monocytes are activated by these AGEs. Ciprofloxacin (CIP), a fluorinated 4-quinolone, is often used clinically to treat infections associated with diabetis due to its antibacterial properties. It also modulates immune responses in human peripheral blood mononuclear cells (PBMC) therefore we investigated the involvement of AGEs in these effects. Experimental Approach Expression of intercellular adhesion molecule (ICAM)-1, B7.1, B7.2 and CD40 was examined by flow cytometry. The production of tumour necrosis factor (TNF)-α, interferon (IFN)-γ, prostaglandin E 2 (PGE 2) and cAMP were determined by enzyme-linked immunosorbent assay. Cyclooxygenase (COX)-2 expression was determined by Western blot analysis. Lymphocyte proliferation was determined by [ 3H]- thymidine uptake. Key Results CIP induced PGE 2 production in monocytes, irrespective of the presence of AGE-2 and AGE-3, by enhancing COX-2 expression; this led to an elevation of intracellular cAMP in monocytes. Non-selective and selective COX-2 inhibitors, indomethacin and NS398, inhibited CIP-induced PGE 2 and cAMP production. In addition, CIP inhibited AGE-2- and AGE-3-induced expressions of ICAM-1, B7.1, B7.2 and CD40 in monocytes, the production of TNF-α and IFN-γ and lymphocyte proliferation in PBMC. Indomethacin, NS398 and a protein kinase A inhibitor, H89, inhibited the actions of CIP. Conclusions and Implications CIP exerts immunomodulatory activity via PGE 2, implying therapeutic potential of CIP for the treatment of AGE-2- and AGE-3-induced inflammatory responses.",
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AU - Takahashi, H. K.

AU - Liu, K.

AU - Wake, Hidenori

AU - Zhang, J.

AU - Liu, R.

AU - Yoshino, Tadashi

AU - Nishibori, Masahiro

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N2 - Background and Purpose Advanced glycation end products (AGEs) subtypes, proteins or lipids that become glycated after exposure to sugars, can induce complications in diabetes. Among the various AGE subtypes, glyceraldehyde- derived AGE (AGE-2) and glycolaldehyde-derived AGE (AGE-3) are involved in inflammation in diabetic patients; monocytes are activated by these AGEs. Ciprofloxacin (CIP), a fluorinated 4-quinolone, is often used clinically to treat infections associated with diabetis due to its antibacterial properties. It also modulates immune responses in human peripheral blood mononuclear cells (PBMC) therefore we investigated the involvement of AGEs in these effects. Experimental Approach Expression of intercellular adhesion molecule (ICAM)-1, B7.1, B7.2 and CD40 was examined by flow cytometry. The production of tumour necrosis factor (TNF)-α, interferon (IFN)-γ, prostaglandin E 2 (PGE 2) and cAMP were determined by enzyme-linked immunosorbent assay. Cyclooxygenase (COX)-2 expression was determined by Western blot analysis. Lymphocyte proliferation was determined by [ 3H]- thymidine uptake. Key Results CIP induced PGE 2 production in monocytes, irrespective of the presence of AGE-2 and AGE-3, by enhancing COX-2 expression; this led to an elevation of intracellular cAMP in monocytes. Non-selective and selective COX-2 inhibitors, indomethacin and NS398, inhibited CIP-induced PGE 2 and cAMP production. In addition, CIP inhibited AGE-2- and AGE-3-induced expressions of ICAM-1, B7.1, B7.2 and CD40 in monocytes, the production of TNF-α and IFN-γ and lymphocyte proliferation in PBMC. Indomethacin, NS398 and a protein kinase A inhibitor, H89, inhibited the actions of CIP. Conclusions and Implications CIP exerts immunomodulatory activity via PGE 2, implying therapeutic potential of CIP for the treatment of AGE-2- and AGE-3-induced inflammatory responses.

AB - Background and Purpose Advanced glycation end products (AGEs) subtypes, proteins or lipids that become glycated after exposure to sugars, can induce complications in diabetes. Among the various AGE subtypes, glyceraldehyde- derived AGE (AGE-2) and glycolaldehyde-derived AGE (AGE-3) are involved in inflammation in diabetic patients; monocytes are activated by these AGEs. Ciprofloxacin (CIP), a fluorinated 4-quinolone, is often used clinically to treat infections associated with diabetis due to its antibacterial properties. It also modulates immune responses in human peripheral blood mononuclear cells (PBMC) therefore we investigated the involvement of AGEs in these effects. Experimental Approach Expression of intercellular adhesion molecule (ICAM)-1, B7.1, B7.2 and CD40 was examined by flow cytometry. The production of tumour necrosis factor (TNF)-α, interferon (IFN)-γ, prostaglandin E 2 (PGE 2) and cAMP were determined by enzyme-linked immunosorbent assay. Cyclooxygenase (COX)-2 expression was determined by Western blot analysis. Lymphocyte proliferation was determined by [ 3H]- thymidine uptake. Key Results CIP induced PGE 2 production in monocytes, irrespective of the presence of AGE-2 and AGE-3, by enhancing COX-2 expression; this led to an elevation of intracellular cAMP in monocytes. Non-selective and selective COX-2 inhibitors, indomethacin and NS398, inhibited CIP-induced PGE 2 and cAMP production. In addition, CIP inhibited AGE-2- and AGE-3-induced expressions of ICAM-1, B7.1, B7.2 and CD40 in monocytes, the production of TNF-α and IFN-γ and lymphocyte proliferation in PBMC. Indomethacin, NS398 and a protein kinase A inhibitor, H89, inhibited the actions of CIP. Conclusions and Implications CIP exerts immunomodulatory activity via PGE 2, implying therapeutic potential of CIP for the treatment of AGE-2- and AGE-3-induced inflammatory responses.

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KW - cyclic adenosine monophosphate

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KW - peripheral blood mononuclear cells

KW - prostaglandins E2

KW - protein kinase A

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