Xia Mengling, Xu Hui, Dai Wei, Zhu Cong, Wu Liqin, Yan Sunshun, Ge Xiangting, Zhou Wangfeng, Chen Cuicui, Dai Yuanrong
a Department of Pulmonary Medicine , Hangzhou Hospital of Traditional Chinese Medicine , Hangzhou , China.
b Department of Pulmonary Medicine , the Second Affiliated Hospital of Wenzhou Medical University , Wenzhou , China.
J Asthma. 2018 Apr;55(4):337-344. doi: 10.1080/02770903.2017.1337788. Epub 2017 Oct 11.
Cigarette smoke is well known to worsen asthma symptoms in asthmatic patients and to make them refractory to treatment, but the underling molecular mechanism is unclear. We hypothesized that cigarette smoke can reduce the expression of HDAC2 in asthma and the process was achieved by activating the PI3K-δ/Akt signaling pathway. We further hypothesized that roxithromycin (RXM) can alleviate the impacts by cigarette smoke.
A murine model of asthma induced by ovalbumin (OVA) and cigarette smoke has been established. The infiltration of inflammatory cells and inflammatory factors was examined in this model. Finally, we evaluated the expression of HDAC2, Akt phosphorylation levels, and the effects of RXM treatment on the model described earlier.
Cigarette smoke exposure reduced HDAC2 protein expression by enhancing the phosphorylation of Akt in PI3K-δ/Akt signaling pathway. Furthermore, RMX reduced the airway inflammation and improved the level of expression of HDAC2 in the cigarette smoke-exposed asthma mice.
This study provides a novel insight into the mechanism of cigarette smoke exposure in asthma and the effects of RXM treatment on this condition. These results may be helpful for treating refractory asthma and emphasizing the need for a smoke-free environment for asthmatic patients.
众所周知，香烟烟雾会加重哮喘患者的哮喘症状并使其对治疗产生耐药性，但其潜在的分子机制尚不清楚。我们推测香烟烟雾会降低哮喘中HDAC2的表达，且该过程是通过激活PI3K-δ/Akt信号通路实现的。我们进一步推测罗红霉素（RXM）可以减轻香烟烟雾的影响。
建立了卵清蛋白（OVA）和香烟烟雾诱导的小鼠哮喘模型。在此模型中检测炎症细胞和炎症因子的浸润情况。最后，我们评估了HDAC2的表达、Akt磷酸化水平以及RXM治疗对上述模型的影响。
暴露于香烟烟雾通过增强PI3K-δ/Akt信号通路中Akt的磷酸化来降低HDAC2蛋白表达。此外，RMX减轻了香烟烟雾暴露的哮喘小鼠的气道炎症，并提高了HDAC2的表达水平。
本研究为香烟烟雾暴露在哮喘中的作用机制以及RXM治疗对此病症的影响提供了新的见解。这些结果可能有助于治疗难治性哮喘，并强调哮喘患者需要无烟环境。
