Effect of nicotine on advanced glycation end product-induced immune response in human monocytes

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


9 被引用数 (Scopus)


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-(pbromocinnamyl-amino)ethyl]-5-isoquinolinesulfonamide dihydrochloride (H89). These results indicate that the mechanism of action of nicotine may be partially via endogenous PGE2 production.

ジャーナルJournal of Pharmacology and Experimental Therapeutics
出版ステータスPublished - 3月 2010

ASJC Scopus subject areas

  • 分子医療
  • 薬理学


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