Prostaglandin E2 inhibits advanced glycation end product-induced adhesion molecule expression, cytokine production, and lymphocyte proliferation in human peripheral blood mononuclear cells

Hideo Kohka Takahashi, Keyue Liu, Hidenori Wake, Shuji Mori, Jiyong Zhang, Rui Liu, Tadashi Yoshino, Masahiro Nishibori

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Abstract

Advanced glycation end product (AGE) subtypes, proteins or lipids that become glycated after exposure to sugars, induce complications in diabetes. Among the various AGE subtypes, glyceraldehyde-derived AGE (AGE-2) and glycolaldehyde-derived AGE (AGE-3) have been indicated to play roles in inflammation in diabetic patients. The engagement of AGEs and receptor for AGEs activates monocytes. Because the engagement of intercellular adhesion molecule-1 (ICAM-1), B7.1, B7.2, and CD40 on monocytes with their ligands on T cells plays roles in cytokine production, we investigated the effects of AGE-2 and AGE-3 on the expressions of ICAM-1, B7.1, B7.2, and CD40 on monocytes, the production of interferon γ and tumor necrosis factor α, and the lymphocyte proliferation in human peripheral blood mononuclear cells and their modulation by prostaglandin E2 (PGE2). AGE-2 and AGE-3 induced the expressions of adhesion molecule, the cytokine production, and the lymphocyte proliferation. PGE2 concentration-dependently inhibited the actions of AGE-2 and AGE-3. The effects of PGE2 were mimicked by an E-prostanoid (EP)2-receptor agonist, 11,15-O-dimethyl prostaglandin E2 (ONO-AE1-259-01), and an EP4 receptor agonist, 16-(3-methoxymethyl)phenyl-ω-tetranor-3,7-dithia prostaglandin E 1 (ONO-AE1-329). An EP2-receptor antagonist, 6-isopropoxy-9-oxaxanthene-2-carboxylic acid (AH6809), and an EP 4-receptor antagonist, (4Z)-7-[(rel-1S,2S,5R)-5-(1,1′-biphenyl- 4-yl)methoxy)-2-(4-morpholinyl)-3-oxocyclopentyl]-4-heptenoic acid (AH23848), inhibited the actions of PGE2. The stimulation of EP2 and EP4 receptors is reported to increase cAMP levels. The effects of PGE2 were reversed by a protein kinase A (PKA) inhibitor, H89, and mimicked by a dibutyryl cAMP and an adenylate cyclase activator, forskolin. These results as a whole indicated that PGE2 inhibited the actions of AGE-2 and AGE-3 via EP2/EP4 receptors and the cAMP/PKA pathway.

Original languageEnglish
Pages (from-to)656-670
Number of pages15
JournalJournal of Pharmacology and Experimental Therapeutics
Volume331
Issue number2
DOIs
Publication statusPublished - Nov 2009

Fingerprint

Advanced Glycosylation End Products
Dinoprostone
Blood Cells
Lymphocytes
Cytokines
Monocytes
Intercellular Adhesion Molecule-1
Cyclic AMP-Dependent Protein Kinases
Prostaglandins
Cyclic AMP Receptors
Glyceraldehyde
Colforsin
Diabetes Complications
Protein Kinase Inhibitors
Carboxylic Acids
Prostaglandins E
Adenylyl Cyclases
Interferons

ASJC Scopus subject areas

  • Pharmacology
  • Molecular Medicine
  • Medicine(all)

Cite this

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title = "Prostaglandin E2 inhibits advanced glycation end product-induced adhesion molecule expression, cytokine production, and lymphocyte proliferation in human peripheral blood mononuclear cells",
abstract = "Advanced glycation end product (AGE) subtypes, proteins or lipids that become glycated after exposure to sugars, induce complications in diabetes. Among the various AGE subtypes, glyceraldehyde-derived AGE (AGE-2) and glycolaldehyde-derived AGE (AGE-3) have been indicated to play roles in inflammation in diabetic patients. The engagement of AGEs and receptor for AGEs activates monocytes. Because the engagement of intercellular adhesion molecule-1 (ICAM-1), B7.1, B7.2, and CD40 on monocytes with their ligands on T cells plays roles in cytokine production, we investigated the effects of AGE-2 and AGE-3 on the expressions of ICAM-1, B7.1, B7.2, and CD40 on monocytes, the production of interferon γ and tumor necrosis factor α, and the lymphocyte proliferation in human peripheral blood mononuclear cells and their modulation by prostaglandin E2 (PGE2). AGE-2 and AGE-3 induced the expressions of adhesion molecule, the cytokine production, and the lymphocyte proliferation. PGE2 concentration-dependently inhibited the actions of AGE-2 and AGE-3. The effects of PGE2 were mimicked by an E-prostanoid (EP)2-receptor agonist, 11,15-O-dimethyl prostaglandin E2 (ONO-AE1-259-01), and an EP4 receptor agonist, 16-(3-methoxymethyl)phenyl-ω-tetranor-3,7-dithia prostaglandin E 1 (ONO-AE1-329). An EP2-receptor antagonist, 6-isopropoxy-9-oxaxanthene-2-carboxylic acid (AH6809), and an EP 4-receptor antagonist, (4Z)-7-[(rel-1S,2S,5R)-5-(1,1′-biphenyl- 4-yl)methoxy)-2-(4-morpholinyl)-3-oxocyclopentyl]-4-heptenoic acid (AH23848), inhibited the actions of PGE2. The stimulation of EP2 and EP4 receptors is reported to increase cAMP levels. The effects of PGE2 were reversed by a protein kinase A (PKA) inhibitor, H89, and mimicked by a dibutyryl cAMP and an adenylate cyclase activator, forskolin. These results as a whole indicated that PGE2 inhibited the actions of AGE-2 and AGE-3 via EP2/EP4 receptors and the cAMP/PKA pathway.",
author = "Takahashi, {Hideo Kohka} and Keyue Liu and Hidenori Wake and Shuji Mori and Jiyong Zhang and Rui Liu and Tadashi Yoshino and Masahiro Nishibori",
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month = "11",
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language = "English",
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pages = "656--670",
journal = "Journal of Pharmacology and Experimental Therapeutics",
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T1 - Prostaglandin E2 inhibits advanced glycation end product-induced adhesion molecule expression, cytokine production, and lymphocyte proliferation in human peripheral blood mononuclear cells

AU - Takahashi, Hideo Kohka

AU - Liu, Keyue

AU - Wake, Hidenori

AU - Mori, Shuji

AU - Zhang, Jiyong

AU - Liu, Rui

AU - Yoshino, Tadashi

AU - Nishibori, Masahiro

PY - 2009/11

Y1 - 2009/11

N2 - Advanced glycation end product (AGE) subtypes, proteins or lipids that become glycated after exposure to sugars, induce complications in diabetes. Among the various AGE subtypes, glyceraldehyde-derived AGE (AGE-2) and glycolaldehyde-derived AGE (AGE-3) have been indicated to play roles in inflammation in diabetic patients. The engagement of AGEs and receptor for AGEs activates monocytes. Because the engagement of intercellular adhesion molecule-1 (ICAM-1), B7.1, B7.2, and CD40 on monocytes with their ligands on T cells plays roles in cytokine production, we investigated the effects of AGE-2 and AGE-3 on the expressions of ICAM-1, B7.1, B7.2, and CD40 on monocytes, the production of interferon γ and tumor necrosis factor α, and the lymphocyte proliferation in human peripheral blood mononuclear cells and their modulation by prostaglandin E2 (PGE2). AGE-2 and AGE-3 induced the expressions of adhesion molecule, the cytokine production, and the lymphocyte proliferation. PGE2 concentration-dependently inhibited the actions of AGE-2 and AGE-3. The effects of PGE2 were mimicked by an E-prostanoid (EP)2-receptor agonist, 11,15-O-dimethyl prostaglandin E2 (ONO-AE1-259-01), and an EP4 receptor agonist, 16-(3-methoxymethyl)phenyl-ω-tetranor-3,7-dithia prostaglandin E 1 (ONO-AE1-329). An EP2-receptor antagonist, 6-isopropoxy-9-oxaxanthene-2-carboxylic acid (AH6809), and an EP 4-receptor antagonist, (4Z)-7-[(rel-1S,2S,5R)-5-(1,1′-biphenyl- 4-yl)methoxy)-2-(4-morpholinyl)-3-oxocyclopentyl]-4-heptenoic acid (AH23848), inhibited the actions of PGE2. The stimulation of EP2 and EP4 receptors is reported to increase cAMP levels. The effects of PGE2 were reversed by a protein kinase A (PKA) inhibitor, H89, and mimicked by a dibutyryl cAMP and an adenylate cyclase activator, forskolin. These results as a whole indicated that PGE2 inhibited the actions of AGE-2 and AGE-3 via EP2/EP4 receptors and the cAMP/PKA pathway.

AB - Advanced glycation end product (AGE) subtypes, proteins or lipids that become glycated after exposure to sugars, induce complications in diabetes. Among the various AGE subtypes, glyceraldehyde-derived AGE (AGE-2) and glycolaldehyde-derived AGE (AGE-3) have been indicated to play roles in inflammation in diabetic patients. The engagement of AGEs and receptor for AGEs activates monocytes. Because the engagement of intercellular adhesion molecule-1 (ICAM-1), B7.1, B7.2, and CD40 on monocytes with their ligands on T cells plays roles in cytokine production, we investigated the effects of AGE-2 and AGE-3 on the expressions of ICAM-1, B7.1, B7.2, and CD40 on monocytes, the production of interferon γ and tumor necrosis factor α, and the lymphocyte proliferation in human peripheral blood mononuclear cells and their modulation by prostaglandin E2 (PGE2). AGE-2 and AGE-3 induced the expressions of adhesion molecule, the cytokine production, and the lymphocyte proliferation. PGE2 concentration-dependently inhibited the actions of AGE-2 and AGE-3. The effects of PGE2 were mimicked by an E-prostanoid (EP)2-receptor agonist, 11,15-O-dimethyl prostaglandin E2 (ONO-AE1-259-01), and an EP4 receptor agonist, 16-(3-methoxymethyl)phenyl-ω-tetranor-3,7-dithia prostaglandin E 1 (ONO-AE1-329). An EP2-receptor antagonist, 6-isopropoxy-9-oxaxanthene-2-carboxylic acid (AH6809), and an EP 4-receptor antagonist, (4Z)-7-[(rel-1S,2S,5R)-5-(1,1′-biphenyl- 4-yl)methoxy)-2-(4-morpholinyl)-3-oxocyclopentyl]-4-heptenoic acid (AH23848), inhibited the actions of PGE2. The stimulation of EP2 and EP4 receptors is reported to increase cAMP levels. The effects of PGE2 were reversed by a protein kinase A (PKA) inhibitor, H89, and mimicked by a dibutyryl cAMP and an adenylate cyclase activator, forskolin. These results as a whole indicated that PGE2 inhibited the actions of AGE-2 and AGE-3 via EP2/EP4 receptors and the cAMP/PKA pathway.

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