PT  - JOURNAL ARTICLE
AU  - Hidenori Wake
AU  - Hideo Kohka Takahashi
AU  - Shuji Mori
AU  - Keyue Liu
AU  - Tadashi Yoshino
AU  - Masahiro Nishibori
TI  - Histamine Inhibits Advanced Glycation End Products-Induced Adhesion Molecule Expression on Human Monocytes
AID  - 10.1124/jpet.109.155960
DP  - 2009 Sep 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 826--833
VI  - 330
IP  - 3
4099  - http://jpet.aspetjournals.org/content/330/3/826.short
4100  - http://jpet.aspetjournals.org/content/330/3/826.full
SO  - J Pharmacol Exp Ther2009 Sep 01; 330
AB  - 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-γ 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. The American Society for Pharmacology and Experimental Therapeutics