Nicotine of unprecedented concentrations and purity is being inhaled by those using commercially available electronic nicotine delivery systems (ENDS). The consequences of this route of self-administration on the immunological response to inhaled allergens are not known. In mice, sensitization and inhalation challenge with the common environmental house dust mite (HDM) allergen is an experimental model of this response. When mice were exposed to twice-daily, 5 days/week, for eight weeks of aerosolized nicotine-base (aeroNic) the HDM-induced recruitment of eosinophils (EOS) was substantially reduced as measured in bronchial alveolar lavage fluid (BALF). Oral nicotine administration had no effect. HDM challenge in the presence of nicotinic receptor subtype alpha7 (α7) specific Type-1 positive allosteric modulators (PAM) was alone sufficient to suppress EOS. RNA analysis of alveolar macrophages (AM) collected from BALF after HDM challenge of aeroNic revealed that α7 activation strongly suppresses initiation of Ccl24 (eotaxin2) transcription. To examine possible cellular signaling mechanisms coupling alpha7 to Ccl24 transcription, an AM culture model system was used. In AM cultures of freshly collected BALF Ccl24 transcription was robustly activated by a mixture of IL-4 and IL-10, and this was suppressed by co-application of Type-1 PAMs through a pathway that requires p38MAPKinase but is independent of Jak2. These results suggest that the EOS response to HDM inhaled allergen is subject to modulation through activation of the α7 receptor and suggests that the allergic response may be substantially modified in ENDS users.

中文翻译：

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吸入雾化尼古丁抑制肺对屋尘螨过敏原的嗜酸性反应。

那些使用市售电子尼古丁传递系统 (ENDS) 的人吸入了前所未有的浓度和纯度的尼古丁。这种自我给药途径对吸入过敏原的免疫反应的后果尚不清楚。在小鼠中，常见环境屋尘螨 (HDM) 过敏原的致敏和吸入挑战是这种反应的实验模型。当小鼠每天接触两次，每周 5 天，连续八周雾化尼古丁碱 (aeroNic) 时，如在支气管肺泡灌洗液 (BALF) 中测量的那样，HDM 诱导的嗜酸性粒细胞 (EOS) 募集显着减少。口服尼古丁给药没有效果。在存在烟碱受体亚型 α7 (α7) 特异性 1 型正变构调节剂 (PAM) 的情况下进行 HDM 挑战就足以抑制 EOS。对 aeroNic 进行 HDM 挑战后从 BALF 收集的肺泡巨噬细胞 (AM) 的 RNA 分析显示，α7 激活强烈抑制 Ccl24 (eotaxin2) 转录的启动。为了检查将 alpha7 耦合到 Ccl24 转录的可能的细胞信号机制，使用了 AM 培养模型系统。在新鲜收集的 BALF Ccl24 的 AM 培养物中，IL-4 和 IL-10 的混合物强烈激活了这一点，这被 1 型 PAM 通过需要 p38MAPKinase 但独立于 Jak2 的途径共同应用所抑制。