Effect of Nicotine on Advanced Glycation End Product-Induced Immune Response in Human Monocytes
Effect of Nicotine on Advanced Glycation End Product-Induced Immune Response in Human Monocytes
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DOI：
10.1124/jpet.109.160861
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发表时间：
2010-03
影响因子：
3.5
通讯作者：
Hideo Takahashi;Keyue Liu;H. Wake;S. Mori;Jiyong Zhang;Rui Liu;T. Yoshino;M. Nishibori
中科院分区：
文献类型：
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作者：
Hideo Takahashi;Keyue Liu;H. Wake;S. Mori;Jiyong Zhang;Rui Liu;T. Yoshino;M. Nishibori
单核细胞上粘附分子表达的上调增强了与T细胞的细胞间相互作用，导致细胞因子产生。晚期糖基化终产物（AGEs）是蛋白质/脂质的修饰，在与醛糖接触后非酶促糖化。在AGEs的不同亚型中，甘油二酸酯衍生的AGE（AGE-2）和乙醇酸酯衍生的AGE（AGE-3）可诱导单核细胞表达细胞间粘附分子-1、B7.1、B7.2和CD 40，产生γ-干扰素和肿瘤坏死因子-α，并促进淋巴细胞增殖。据报道，尼古丁通过烟碱乙酰胆碱受体α7亚基（α7-nAChR）抑制单核细胞的活化。在本研究中，我们发现尼古丁抑制AGE-2和AGE-3的作用。非选择性和选择性α7-nAChR拮抗剂美加明和α-银环蛇毒素可逆转尼古丁的抑制作用，表明α7-nAChR刺激参与其中。尼古丁诱导表达的环氧合酶-2，前列腺素E2（PGE 2），cAMP的存在和不存在的AGE-2和AGE-3。已知PGE 2激活EP 2/EP 4受体，增加cAMP水平和蛋白激酶A（PKA）活性。尼古丁的作用可被EP 2受体拮抗剂AH 6809、EP 4受体拮抗剂AH 23848和PKA抑制剂N-[2-（对溴肉桂酰氨基）乙基]-5-异喹啉磺酰胺二盐酸盐（H89）部分逆转。这些结果表明，尼古丁的作用机制可能部分通过内源性PGE 2的产生。
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.