Inhibitory effects of nicotine derived from cigarette smoke on thymic stromal lymphopoietin production in epidermal keratinocytes
Inhibitory effects of nicotine derived from cigarette smoke on thymic stromal lymphopoietin production in epidermal keratinocytes
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DOI：
10.1016/j.cellimm.2016.01.001
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发表时间：
2016-04-01
影响因子：
4.3
通讯作者：
Hirasawa, Noriyasu
中科院分区：
文献类型：
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作者：
Dong, Jiangxu;Segawa, Ryosuke;Hirasawa, Noriyasu
胸腺基质淋巴生成素（TSLP）被认为是导致特应性皮炎（AD）发病的主要因素。吸烟是过敏的加重因素，但据报道可以降低患阿尔茨海默病的风险。在本研究中，我们评估了香烟烟雾提取物中主要成分尼古丁在调节TSLP表达中的作用及其潜在的作用机制。我们发现尼古丁显著抑制12- o - tetradecanoylphorol -13-acetate （TPA）诱导的BALB/c小鼠和小鼠角质形成细胞系PAM212中TSLP的表达。经α - 7烟碱乙酰胆碱受体（α - 7 nAChR）拮抗剂、amp活化蛋白激酶（AMPK）抑制剂和磷酸肌肽3激酶（PI3K）抑制剂预处理后，烟碱对TSLP产生的抑制作用被消除。同样的抑制剂消除了尼古丁对核因子κ B （nf - κ B）活化的抑制作用。这些结果表明，尼古丁通过α 7 nAChR-PI3K-AMPK信号通路抑制NF-kappa B的激活，从而抑制TSLP的表达。(C) 2016 Elsevier Inc.版权所有。
Thymic stromal lymphopoietin (TSLP) is regarded as the main factor responsible for the pathogenesis of atopic dermatitis (AD). Cigarette smoke is an aggravating factor for allergies, but has been reported to decrease the risk of AD. In the present study, we evaluated the role of nicotine, the main constituent in cigarette smoke extract, and its underlying mechanism of action in the regulation of TSLP expression. We found that nicotine significantly inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced TSLP expression in BALB/c mice and the mouse keratinocyte cell line PAM212. Nicotine inhibition of TSLP production was abolished by pretreatments with alpha 7 nicotinic acetylcholine receptor (alpha 7 nAChR) antagonists, AMP-activated protein kinase (AMPK) inhibitor, and phosphoinositide 3-kinase (PI3K) inhibitors. The same inhibitors abolished inhibition of nuclear factor-kappa B (NF-kappa B) activation by nicotine. These results suggest that nicotine inhibits the expression of TSLP by suppressing the activation of NF-kappa B through the alpha 7 nAChR-PI3K-AMPK signaling pathway. (C) 2016 Elsevier Inc. All rights reserved.