The Tobacco Smoke Component, Acrolein, Suppresses Innate Macrophage Responses by Direct Alkylation of c-Jun N-Terminal Kinase
The Tobacco Smoke Component, Acrolein, Suppresses Innate Macrophage Responses by Direct Alkylation of c-Jun N-Terminal Kinase
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DOI：
10.1165/rcmb.2011-0134oc
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发表时间：
2012-01-01
影响因子：
6.4
通讯作者：
van der Vliet, Albert
中科院分区：
文献类型：
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作者：
Hristova, Milena;Spiess, Page C.;van der Vliet, Albert
呼吸道先天免疫系统经常受到烟草烟雾暴露的损害，以前的研究表明，丙烯醛，烟草烟雾中的反应性亲电体，可能有助于吸烟的免疫抑制作用。暴露于丙烯醛的小鼠在类似于香烟烟雾中的浓度（5 ppm，4小时）显着抑制肺泡巨噬细胞对细菌LPS的反应，减少诱导一氧化氮合酶2，TNF-α，和IL-12 p40。骨髓源性巨噬细胞或MH-S巨噬细胞的机制研究表明，丙烯醛（1-30 μ M）减弱了这些LPS介导的先天性反应与细胞谷胱甘肽的耗竭，虽然谷胱甘肽耗竭本身并不完全负责这些免疫抑制作用。丙烯醛的抑制作用在急性暴露后最为显著（
The respiratory innate immune system is often compromised by tobacco smoke exposure, and previous studies have indicated that acrolein, a reactive electrophile in tobacco smoke, may contribute to the immunosuppressive effects of smoking. Exposure of mice to acrolein at concentrations similar to those in cigarette smoke (5ppm, 4h) significantly suppressed alveolarmacrophage responses to bacterial LPS, indicated by reduced induction of nitric oxide synthase 2, TNF-alpha, and IL-12p40. Mechanistic studies with bone marrow-derived macrophages or MH-S macrophages demonstrated that acrolein (1-30 mu M) attenuated these LPS-mediated innate responses in association with depletion of cellular glutathione, although glutathione depletion itself was not fully responsible for these immunosuppressive effects. Inhibitory actions of acroleinwere most prominent after acute exposure (