Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND, USA.
Department of Anesthesiology and Perioperative Medicine, USA.
Arch Biochem Biophys. 2021 Jul 30;706:108897. doi: 10.1016/j.abb.2021.108897. Epub 2021 May 15.
Diseases such as asthma are exacerbated by inflammation, cigarette smoke and even nicotine delivery devices such as e-cigarettes. However, there is currently little information on how nicotine affects airways, particularly in humans, and changes in the context of inflammation or asthma. Here, a longstanding assumption is that airway smooth muscle (ASM) that is key to bronchoconstriction has muscarinic receptors while nicotinic receptors (nAChRs) are only on airway neurons. In this study, we tested the hypothesis that human ASM expresses α7nAChR and explored its profile in inflammation and asthma using ASM of non-asthmatics vs. mild-moderate asthmatics. mRNA and western analysis showed the α7 subunit is most expressed in ASM cells and further increased in asthmatics and smokers, or by exposure to nicotine, cigarette smoke or pro-inflammatory cytokines TNFα and IL-13. In these effects, signaling pathways relevant to asthma such as NFκB, AP-1 and CREB are involved. These novel data demonstrate the expression of α7nAChR in human ASM and suggest their potential role in asthma pathophysiology in the context of nicotine exposure.
哮喘等疾病会因炎症、香烟烟雾甚至电子烟等尼古丁输送装置而加重。然而，目前关于尼古丁如何影响气道，特别是在人类中的影响，以及在炎症或哮喘的背景下的变化，信息还很少。在这里，人们长期以来一直认为，气道平滑肌（ASM）是支气管收缩的关键，它具有毒蕈碱受体，而烟碱受体（nAChRs）仅存在于气道神经元上。在这项研究中，我们检验了这样一个假设，即人类 ASM 表达α7nAChR，并使用非哮喘患者与轻度至中度哮喘患者的 ASM 来研究其在炎症和哮喘中的特征。mRNA 和 Western blot 分析表明，α7 亚基在 ASM 细胞中表达最多，并在哮喘患者和吸烟者中进一步增加，或通过暴露于尼古丁、香烟烟雾或促炎细胞因子 TNFα 和 IL-13 增加。在这些作用中，涉及哮喘的信号通路，如 NFκB、AP-1 和 CREB，也参与其中。这些新的数据表明，α7nAChR 在人类 ASM 中的表达，并表明其在尼古丁暴露背景下的哮喘病理生理学中的潜在作用。
