Department of Respiratory Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China.
Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China.
Mediators Inflamm. 2017;2017:6506953. doi: 10.1155/2017/6506953. Epub 2017 Aug 29.
IRAK-M, negatively regulating Toll-like receptor, is shown the dual properties in the varied disease contexts. We studied the effect of IRAK-M deficiency on cigarette smoking- (CS-) induced airway inflammation under acute or subacute conditions in a mouse model.
A number of cellular and molecular techniques were used to detect the differences between IRAK-M knockout (KO) and wild type (WT) mice exposed to 3-day or 7-week CS.
Airway inflammation was comparable between IRAK-M KO and WT mice under 3-day CS exposure. Upon short-term CS exposure and lipopolysaccharide (LPS) inhalation, IRAK-M KO mice demonstrated worse airway inflammation, significantly higher percentage of Th17 cells and concentrations of proinflammatory cytokines in the lungs, and significantly elevated expression of costimulatory molecules CD40 and CD86 by lung dendritic cells (DCs) or macrophages. Conversely, 7-week CS exposed IRAK-M KO mice demonstrated significantly attenuated airway inflammation, significantly lower concentrations of proinflammatory cytokines in the lungs, significantly increased percentage of Tregs, and lower expression of CD11b and CD86 by lung DCs or macrophages.
IRAK-M plays distinctive effect on CS-induced airway inflammation, and influences Treg/Th17 balance and expression of costimulatory molecules by DCs and macrophages, depending on duration and intensity of stimulus.
负向调控 Toll 样受体的 IRAK-M 在不同疾病环境中表现出双重特性。我们在小鼠模型中研究了 IRAK-M 缺失对急性或亚急性吸烟（CS）诱导的气道炎症的影响。
使用多种细胞和分子技术来检测在接受 3 天 CS 暴露的 IRAK-M 敲除（KO）和野生型（WT）小鼠之间的差异。
在 3 天 CS 暴露下，气道炎症在 IRAK-M KO 和 WT 小鼠之间无明显差异。在短期 CS 暴露和脂多糖（LPS）吸入后，IRAK-M KO 小鼠表现出更严重的气道炎症，肺中 Th17 细胞的比例和促炎细胞因子的浓度显著升高，肺树突状细胞（DC）或巨噬细胞表达的共刺激分子 CD40 和 CD86 显著升高。相反，在接受 7 周 CS 暴露的 IRAK-M KO 小鼠中，气道炎症明显减轻，肺中促炎细胞因子的浓度显著降低，Treg 的比例显著增加，肺 DC 或巨噬细胞表达的 CD11b 和 CD86 显著降低。
IRAK-M 对 CS 诱导的气道炎症具有独特的作用，并且根据刺激的持续时间和强度影响 DC 和巨噬细胞中 Treg/Th17 平衡和共刺激分子的表达。
