RT Journal Article
SR Electronic
T1 Effect of Nicotine on Advanced Glycation End Product-Induced Immune Response in Human Monocytes
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 1013
OP 1021
DO 10.1124/jpet.109.160861
VO 332
IS 3
A1 Hideo Kohka Takahashi
A1 Keyue Liu
A1 Hidenori Wake
A1 Shuji Mori
A1 Jiyong Zhang
A1 Rui Liu
A1 Tadashi Yoshino
A1 Masahiro Nishibori
YR 2010
UL http://jpet.aspetjournals.org/content/332/3/1013.abstract
AB The up-regulation of adhesion molecule expressions on monocytes enhances cell-to-cell interactions with T cells, leading to cytokine production. 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) induce the expressions of intercellular adhesion molecule-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. Nicotine is reported to inhibit the activation of monocytes via nicotinic acetylcholine receptor α7 subunit (α7-nAChR). In the present study, we found that nicotine inhibited the actions of AGE-2 and AGE-3. A nonselective and selective α7-nAChR antagonist, mecamylamine and α-bungarotoxin, reversed the inhibitory effects of nicotine, suggesting the involvement of α7-nAChR stimulation. Nicotine induced the expression of cyclooxygenase-2, prostaglandin E2 (PGE2), and cAMP in the presence and absence of AGE-2 and AGE-3. PGE2 is known to activate the EP2/EP4 receptor, increasing the cAMP level and protein kinase A (PKA) activity. The actions of nicotine were reversed in part by an EP2-receptor antagonist, AH6809, an EP4-receptor antagonist, AH23848, and a PKA inhibitor, N-[2-(p-bromocinnamyl-amino)ethyl]-5-isoquinolinesulfonamide dihydrochloride (H89). These results indicate that the mechanism of action of nicotine may be partially via endogenous PGE2 production.Copyright © 2010 by The American Society for Pharmacology and Experimental Therapeutics