IL-24调控巨噬细胞极化介导气道炎症在过敏性哮喘小鼠中的作用  

Role of IL-24 in regulating macrophage polarization and airway inflammation in allergic asthmatic mice

作　　者：冯康尼 孟平[1] 张敏[1] 邹小玲[1] 李双 李洪涛[1] 张天托[1] FENG Kang-ni;MENG Ping;ZHANG Min;ZOU Xiao-ling;LI Shuang;LI Hong-tao;ZHANG Tian-tuo(Department of Pulmonary and Critical Care Medicine,The Third Affiliated Hospital of Sun Yat-sen University,Guangzhou 510630,China)

机构地区：[1]中山大学附属第三医院呼吸与危重症医学科,广东广州510630

出　　处：《中国病理生理杂志》2022年第7期1201-1209,共9页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.81970017)。

摘　　要：目的:探讨白细胞介素24(interleukin-24,IL-24)在过敏性哮喘小鼠中调控巨噬细胞表型转变的作用,以期为过敏性哮喘临床治疗提供新的靶点。方法:利用人单核细胞系THP-1和小鼠骨髓来源的巨噬细胞,添加脂多糖或IL-4伴或不伴有IL-24诱导巨噬细胞极化,流式细胞术检测M1和M2型巨噬细胞的比例。将40只雌性BALB/c小鼠(6~8周龄)随机分为对照组、哮喘组、si-IL-24组和si-NC组,每组10只;采用屋尘螨(house dust mite,HDM)提取物滴鼻致敏构建过敏性哮喘小鼠模型,si-IL-24组和si-NC组在过敏原暴露前1 h前分别予si-IL-24和siNC溶液滴鼻,对照组予等体积PBS滴鼻。末次过敏原激发24 h内采用有创小鼠肺功能仪检测气道反应性;免疫组化和Western blot验证si-IL-24的沉默效率;HE染色观察哮喘小鼠肺部炎症浸润情况;流式细胞术分析小鼠肺组织中M1和M2型巨噬细胞的比例。结果:IL-24与IL-4在体外协同促进M2型巨噬细胞极化。哮喘组小鼠肺组织IL-24表达水平较正常组显著增高,且si-IL-24鼻内递送降低哮喘小鼠肺部IL-24的表达水平;HDM诱导的哮喘小鼠肺部炎症以M2巨噬细胞浸润为主;与哮喘组相比,沉默IL-24后小鼠气道反应性降低,肺部炎症浸润程度减轻,肺组织中M2型巨噬细胞比例显著降低。结论:靶向沉默IL-24可减轻过敏性哮喘小鼠哮喘症状,其机制可能与抑制M2型巨噬细胞极化有关。AIM:To investigate the role of interleukin-24(IL-24)in regulating phenotypic transformation of macrophages in allergic asthma mice,and to provide a novel target for clinical treatment of allergic asthma.METHODS:Human monocyte THP-1 cells and mouse bone marrow-derived macrophages were used to induce M1 or M2 phenotype macrophages using lipopolysaccharide or IL-4 with or without IL-24. The proportion of M1 and M2 type macrophages was determined by flow cytometry. Forty female BALB/c mice(6 to 8 weeks old)were randomly divided into control group,asthma group,si-IL-24 group,and si-NC group,with 10 mice per group. The mouse model of allergic asthma was induced by intranasal administration of house dust mite(HDM)extract. The mice in si-IL-24 and si-NC groups were intranasally given si-IL-24 and si-NC solution 1 h before allergen exposure,respectively. The mice in control group received equal volume of PBS intranasally. Airway responsiveness of the mice was detected by invasive pulmonary function instrument within 24 h after the last allergen challenge. The silencing efficiency of si-IL-24 was verified by immunohistochemical staining and Western blot. Pulmonary inflammatory infiltration in asthmatic mice was evaluated by HE staining. The proportion of M1and M2 macrophages in lung tissues of mice were analyzed by flow cytometry.RESULTS:Treatment with IL-24 and IL-4synergistically promoted the polarization of M2 macrophages in vitro. The expression of IL-24 in mouse lung tissues of asthma group was significantly increased compared with normal group,and intranasal delivery of si-IL-24 reduced the level of IL-24 in lung tissues of asthmatic mice. Pulmonary inflammation was mainly infiltrated by M2 macrophages in HDM-induced asthmatic mice. Compared with asthma group,silencing of IL-24 resulted in decreased airway responsiveness and lung inflammatory infiltration,as well as a less proportion of M2 macrophages in the lung tissues.CONCLUSION:Targeted silencing of IL-24 can alleviate asthma symptoms in allergic asthma mice,and

关 键 词：哮喘 白细胞介素24 巨噬细胞极化 

分 类 号：R562.25[医药卫生—呼吸系统] R363.21[医药卫生—内科学]