Zhang Jun-Feng, Li Yi, Zhang Ai-Zhen, He Qian-Qian, Du Yong-Cheng, Cao Wen
Department of Health Statistics, Public Health of Shanxi Medical University, Taiyuan 030001, China.
Publishing house, Chinese Journal of Rheumatology, Taiyuan 030001, China.
J Thorac Dis. 2018 Sep;10(9):5459-5467. doi: 10.21037/jtd.2018.08.124.
Cigarette smoking aggravates the symptoms of asthma, leading to the rapid decline of lung function. Dendritic cells (DCs) and lymphocytes are considered initiating and promoting factors for the airway inflammation reactions of asthma. In addition, activation of CC chemokine receptor 7 (CCR7) by chemokine (C-C motif) ligand (CCL) 19 and 21 promotes DCs and T cells migration to lymphoid tissues during inflammation. We aimed to examine how cigarette smoke affects the expression of CCR7 in the lungs of asthmatic rats and explore the signaling mechanism linking CCR7 expression to exacerbation of symptoms.
Forty Wistar rats were randomized to four groups: control, asthma, smoke exposure, and asthma with smoke exposure groups. A rat asthma model was established by intraperitoneal ovalbumin injection. CCR7 expression was examined with immunohistochemistry and western blotting. The number of airway DCs was determined by OX62 immunohistochemistry. Interferon (INF)-γ, interleukin (IL)-4, CCL19, and CCL21 expression levels in blood and bronchioalveolar lavage fluid (BALF) were determined by enzyme-linked immunosorbent assays (ELISAs).
Tissue CCR7 expression, peripheral blood and BALF CCL19 and CCL21 concentrations, and the number of airway DCs were significantly higher in the asthma with smoke exposure group than the asthma group (P<0.01). In addition, INF-γ expression was decreased and IL-4 increased in the asthma and asthma with smoke exposure groups compared with the control group (P<0.01), and in the asthma with smoke exposure group compared with the asthma group (P<0.01). Expression of CCR7 correlated negatively with INF-γ expression in peripheral blood and BALF (P<0.01), and positively with the airway DCs and IL-4 expression in the peripheral blood and BALF (P<0.01).
Cigarette smoking may aggravate asthma symptoms by attenuating immunity, possibly through CCR7-mediated DCs aggregation in lung tissue.
吸烟会加重哮喘症状，导致肺功能迅速下降。树突状细胞（DCs）和淋巴细胞被认为是哮喘气道炎症反应的起始和促进因素。此外，趋化因子（C-C基序）配体（CCL）19和21对CC趋化因子受体7（CCR7）的激活促进了炎症期间DCs和T细胞向淋巴组织的迁移。我们旨在研究香烟烟雾如何影响哮喘大鼠肺中CCR7的表达，并探索将CCR7表达与症状加重联系起来的信号传导机制。
40只Wistar大鼠随机分为四组：对照组、哮喘组、烟雾暴露组和哮喘合并烟雾暴露组。通过腹腔注射卵清蛋白建立大鼠哮喘模型。采用免疫组织化学和蛋白质印迹法检测CCR7表达。通过OX62免疫组织化学测定气道DCs数量。采用酶联免疫吸附测定法（ELISAs）测定血液和支气管肺泡灌洗液（BALF）中干扰素（INF）-γ、白细胞介素（IL）-4、CCL19和CCL21的表达水平。
哮喘合并烟雾暴露组的组织CCR7表达、外周血和BALF中CCL19和CCL21浓度以及气道DCs数量均显著高于哮喘组（P<0.01）。此外，与对照组相比，哮喘组和哮喘合并烟雾暴露组的INF-γ表达降低，IL-4增加（P<0.01），与哮喘组相比，哮喘合并烟雾暴露组的INF-γ表达降低（P<0.01）。外周血和BALF中CCR7表达与INF-γ表达呈负相关（P<0.01），与外周血和BALF中的气道DCs和IL-4表达呈正相关（P<0.01）。
吸烟可能通过削弱免疫力加重哮喘症状，可能是通过CCR7介导的肺组织中DCs聚集实现的
