Effect of nicotine on advanced glycation end product-induced immune response in human monocytes.
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.
Takahashi
Hideo Kohka
HK
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
Liu
Keyue
K
Wake
Hidenori
H
Mori
Shuji
S
Zhang
Jiyong
J
Liu
Rui
R
Yoshino
Tadashi
T
Nishibori
Masahiro
M
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
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