Aerosolized nicotine from e-cigarettes alters gene expression, increases lung protein permeability, and impairs viral clearance in murine influenza infection.
Aerosolized nicotine from e-cigarettes alters gene expression, increases lung protein permeability, and impairs viral clearance in murine influenza infection.
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DOI：
10.3389/fimmu.2023.1076772
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发表时间：
2023
影响因子：
7.3
通讯作者：
Matthay, Michael A.
中科院分区：
文献类型：
--
作者：
Maishan, Mazharul;Sarma, Aartik;Chun, Lauren F.;Caldera, Saharai;Fang, Xiaohui;Abbott, Jason;Christenson, Stephanie A.;Langelier, Charles R.;Calfee, Carolyn S.;Gotts, Jeffrey E.;Matthay, Michael A.
电子烟的使用迅速增加，作为一种通过加热气雾化传递尼古丁的替代方式。最近的研究表明，含有尼古丁的电子烟气雾剂可以具有免疫抑制和促炎作用，但尚不清楚电子烟和电子烟液体的成分如何影响急性肺损伤和病毒性肺炎引起的急性呼吸窘迫综合征的发展。因此，在这些研究中，小鼠在连续九天内每天接触一小时的气雾剂，这种气雾剂由临床相关的罐式Aspire Aautilus雾化电子液体产生，其中包含植物甘油和丙二醇的混合物(VG/PG)，其中含有或不含有尼古丁。暴露于含有尼古丁的气雾剂可导致临床相关水平的血浆可替宁，一种尼古丁衍生的代谢物，以及远端空气中促炎细胞因子IL-17A、CXCL1和MCP-1的增加。在接触电子烟后，小鼠被鼻腔接种甲型流感病毒(H1N1 PR8株)。在接种后7天(Dpi)，暴露于VG/PG产生的气雾剂和尼古丁加和不加尼古丁的VG/PG产生的气雾剂导致更多流感诱导的致炎细胞因子干扰素-γ、肿瘤坏死因子α、IL-1β、IL-6、IL-17A和单核细胞趋化蛋白-1的产生。与雾化载体VG/PG相比，在雾化尼古丁暴露的小鼠中，远端空气中粘蛋白5亚型AC(MUC5AC)的含量显著低于雾化载体VG/PG，而在流感7dpi时肺对蛋白质和病毒载量的肺通透性显著高于雾化载体VG/PG。此外，尼古丁导致与纤毛功能和液体清除相关的基因相对下调，并在7dpi时增加了促炎途径的表达。这些结果表明：(1)e-液体载体VG/PG增强了对病毒性肺炎的促炎免疫应答；(2)电子烟气雾剂中的尼古丁改变了对病原体的转录反应，钝化了宿主防御机制，增加了肺屏障通透性，降低了流感病毒的清除。总而言之，急性暴露于雾化尼古丁会损害病毒感染的清除，并加剧肺损伤，这一发现对电子烟产品的监管具有意义。
E-cigarette use has rapidly increased as an alternative means of nicotine delivery by heated aerosolization. Recent studies demonstrate nicotine-containing e-cigarette aerosols can have immunosuppressive and pro-inflammatory effects, but it remains unclear how e-cigarettes and the constituents of e-liquids may impact acute lung injury and the development of acute respiratory distress syndrome caused by viral pneumonia. Therefore, in these studies, mice were exposed one hour per day over nine consecutive days to aerosol generated by the clinically-relevant tank-style Aspire Nautilus aerosolizing e-liquid containing a mixture of vegetable glycerin and propylene glycol (VG/PG) with or without nicotine. Exposure to the nicotine-containing aerosol resulted in clinically-relevant levels of plasma cotinine, a nicotine-derived metabolite, and an increase in the pro-inflammatory cytokines IL-17A, CXCL1, and MCP-1 in the distal airspaces. Following the e-cigarette exposure, mice were intranasally inoculated with influenza A virus (H1N1 PR8 strain). Exposure to aerosols generated from VG/PG with and without nicotine caused greater influenza-induced production in the distal airspaces of the pro-inflammatory cytokines IFN-γ, TNFα, IL-1β, IL-6, IL-17A, and MCP-1 at 7 days post inoculation (dpi). Compared to the aerosolized carrier VG/PG, in mice exposed to aerosolized nicotine there was a significantly lower amount of Mucin 5 subtype AC (MUC5AC) in the distal airspaces and significantly higher lung permeability to protein and viral load in lungs at 7 dpi with influenza. Additionally, nicotine caused relative downregulation of genes associated with ciliary function and fluid clearance and an increased expression of pro-inflammatory pathways at 7 dpi. These results show that (1) the e-liquid carrier VG/PG increases the pro-inflammatory immune responses to viral pneumonia and that (2) nicotine in an e-cigarette aerosol alters the transcriptomic response to pathogens, blunts host defense mechanisms, increases lung barrier permeability, and reduces viral clearance during influenza infection. In conclusion, acute exposure to aerosolized nicotine can impair clearance of viral infection and exacerbate lung injury, findings that have implications for the regulation of e-cigarette products.
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宿主对甲型流感病毒感染的免疫反应
影响因子：
7.3
作者：
Chen X;Liu S;Goraya MU;Maarouf M;Huang S;Chen JL
通讯作者：
Chen JL
影响因子：
9.6
作者：
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DOI：
10.3390/ijerph18084079
发表时间：
2021-04-13
影响因子：
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作者：
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通讯作者：
Pérez-Rubio G
影响因子：
10
作者：
Garcia-Arcos I;Geraghty P;Baumlin N;Campos M;Dabo AJ;Jundi B;Cummins N;Eden E;Grosche A;Salathe M;Foronjy R
通讯作者：
Foronjy R
影响因子：
5.4
作者：
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通讯作者：
Hoffman, Steven J.