Histamine inhibits advanced glycation end products-induced adhesion molecule expression on human monocytes.
Advanced glycation end products (AGEs) are modifications of proteins/lipids that become nonenzymatically glycated after contact with aldose sugars. Among various subtypes of AGEs, glyceraldehyde-derived AGE (AGE-2) and glycolaldehyde-derived AGE (AGE-3) are suggested to play roles in inflammation in diabetic patients. Because the engagement of intercellular adhesion molecule (ICAM)-1, B7.1, B7.2, and CD40 on monocytes with their ligands on T cells plays roles in cytokine production, we examined the effects of AGE-2 and AGE-3 on the expression of adhesion molecules and cytokine production in human peripheral blood mononuclear cells (PBMC) and their modulation by histamine in the present study. AGE-2 and AGE-3 induced the expressions of ICAM-1, B7.1, B7.2, and CD40 on monocytes and the production of interferon-gamma in PBMC. Histamine concentration-dependently inhibited the action of AGE-2 and AGE-3. The effects of histamine were antagonized by an H2 receptor antagonist, famotidine, and mimicked by H2/H4 receptor agonists dimaprit and 4-methylhistamine. Histamine induced cAMP production in the presence and absence of AGE-2 and AGE-3. The effects of histamine were reversed by a protein kinase A (PKA) inhibitor, N-[2-(4-bromocinnamylamino)ethyl]-5-isoquinoline (H89), and mimicked by a dibutyryl cAMP and an adenylate cyclase activator, forskolin. These results as a whole indicated that histamine inhibited the AGE-2- and AGE-3-induced adhesion molecule expression and cytokine production via H2 receptors and the cAMP/PKA pathway.
Wake
Hidenori
H
Department of Pharmacology, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
Takahashi
Hideo Kohka
HK
Mori
Shuji
S
Liu
Keyue
K
Yoshino
Tadashi
T
Nishibori
Masahiro
M
D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D049109:Cell Proliferation / Q000187:drug effects; D000242:Cyclic AMP / Q000096:biosynthesis; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D005434:Flow Cytometry; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D006632:Histamine / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011970:Receptors, Histamine H2 / Q000187:drug effects / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology
D015815:Cell Adhesion Molecules; D017127:Glycation End Products, Advanced; D007546:Isoquinolines; D047428:Protein Kinase Inhibitors; D011970:Receptors, Histamine H2; D013449:Sulfonamides; D006632:Histamine; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide