title: Effect of nicotine on advanced glycation end product-induced immune response in human monocytes.
abstract: 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.
authors: Department of Pharmacology, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8558, Japan. kohka611@md.okayama-u.ac.jp
authors: Hideo Kohka
authors: HK
authors: Takahashi
authors: Keyue
authors: K
authors: Liu
authors: Hidenori
authors: H
authors: Wake
authors: Shuji
authors: S
authors: Mori
authors: Jiyong
authors: J
authors: Zhang
authors: Rui
authors: R
authors: Liu
authors: Tadashi
authors: T
authors: Yoshino
authors: Masahiro
authors: M
authors: Nishibori
mesh_terms: D051940:B7-2 Antigen / Q000096:biosynthesis; D019013:CD40 Antigens / Q000096:biosynthesis; D049109:Cell Proliferation; D000242:Cyclic AMP / Q000096:biosynthesis; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D015232:Dinoprostone / Q000096:biosynthesis; D017127:Glycation End Products, Advanced / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000502:physiology; D018078:Receptors, Prostaglandin E / Q000502:physiology; D058307:Receptors, Prostaglandin E, EP2 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: D051940:B7-2 Antigen; D019013:CD40 Antigens; C497964:CD86 protein, human; C579167:Chrna7 protein, human; D017127:Glycation End Products, Advanced; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; C545644:PTGER2 protein, human; C545650:PTGER4 protein, human; D011978:Receptors, Nicotinic; D018078:Receptors, Prostaglandin E; D058307:Receptors, Prostaglandin E, EP2 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype; D014409:Tumor Necrosis Factor-alpha; D064569:alpha7 Nicotinic Acetylcholine Receptor; D018799:Intercellular Adhesion Molecule-1; D009538:Nicotine; D007371:Interferon-gamma; D000242:Cyclic AMP; D051546:Cyclooxygenase 2; D017868:Cyclic AMP-Dependent Protein Kinases; D015232:Dinoprostone