| 19955489 |
Takahashi HK, Liu K, Wake H, Mori S, Zhang J, Liu R, Yoshino T, Nishibori M: Effect of nicotine on advanced glycation end product-induced immune response in human monocytes. J Pharmacol Exp Ther. 2010 Mar;332(3):1013-21. Epub 2009 Dec 2.
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-gamma and tumor necrosis factor-alpha, and the lymphocyte proliferation in human peripheral blood mononuclear cells. Nicotine is reported to inhibit the activation of monocytes via nicotinic acetylcholine receptor alpha7 subunit (alpha7-nAChR). In the present study, we found that nicotine inhibited the actions of AGE-2 and AGE-3. A nonselective and selective alpha7-nAChR antagonist, mecamylamine and alpha-bungarotoxin, reversed the inhibitory effects of nicotine, suggesting the involvement of alpha7-nAChR stimulation. Nicotine induced the expression of cyclooxygenase-2, prostaglandin E (2) (PGE (2)), and cAMP in the presence and absence of AGE-2 and AGE-3. PGE (2) is known to activate the EP (2)/EP (4) receptor, increasing the cAMP level and protein kinase A (PKA) activity. The actions of nicotine were reversed in part by an EP (2)-receptor antagonist, AH6809, an EP (4)-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 PGE (2) production. |
1(0,0,0,1) |