在囊性纤维化中CFTR和免疫功能的二手vape暴露调节和免疫功能
Benjamin L Wisniewski1, Mahesh Shrestha2,3, Dinesh Bojja2,3
1Section of Pediatric Pulmonology & Sleep Medicine, Department of Pediatrics, University of Colorado Anschutz Medical Campus & Children's Hospital Colorado, Aurora, Colorado, United States.
概括
二手电子烟 (e-cig) 暴露会通过降低CF跨膜导电调节器 (CFTR) 功能来损害囊性纤维化 (CF). 电子烟的使用可能会限制CFTR调节器疗法的有效性.
科学领域:
- 肺病学和呼吸系统医学
- 细胞生物学和免疫学
- 药理学和药物发现
背景情况:
- 接触二手烟 (SHSe) 对患有囊性纤维化 (CF) 的人来说是一个已知的威胁,影响呼吸系统和营养健康.
- 电子烟 (e-cig) 的使用正在增加,这引发了人们对二手电子烟蒸汽暴露的担忧,特别是在像CF这样的弱势群体中.
- 电子烟暴露对CFTR功能和CF的免疫反应的影响在很大程度上是未知的,与初级吸烟的确定的风险不同.
研究的目的:
- 调查二手电子烟 (e-cig) 暴露对CFTR表达和功能对囊性纤维化 (CF) 相关的人类细胞的影响.
- 确定电子烟暴露如何影响CF模型中的免疫反应,代谢信号和杀死细菌.
- 评估电子烟暴露是否会干扰CFTR调节器疗法在CF细胞中的疗效.
主要方法:
- 人类CF和非CF血液单细胞衍生的巨细胞 (MDMs) 和支气管上皮细胞 (HBECs) 暴露于风味和无风味的电子烟蒸汽.
- 分析了CFTR表达和功能,杀死细菌,细胞因子信号传递,脂质媒介和细胞代谢.
- 用CFTR调节剂 (elexacaftor/tezacaftor/ivacaftor - ETI) 治疗细胞,以评估电子烟暴露对治疗疗效的影响.
主要成果:
- 电子烟暴露在CF和非CFMDM中显著降低了CFTR表达和功能.
- 电子烟在CFMDM中否定了ETI对CFTR和抗炎PGD2的功能恢复.
- 风味电子烟增加了促炎性细胞因子,并促进了CF MDMs中的糖溶性新陈代谢,而细菌杀死仍然不受影响. HBECs的影响低于MDMs.
结论:
- 电子烟 (e-cig) 暴露会降低巨细胞CFTR表达,并在囊性纤维化 (CF) 模型中降低CFTR调节器的疗效.
- 电子烟暴露促进了巨细胞的炎症和代谢改变状态,可能会加剧CF.
- 电子烟对CF患者来说是一个新兴的公共卫生风险,可能会限制当前和未来CFTR向治疗的好处.
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