Effect of IRAK-M on Airway Inflammation Induced by Cigarette Smoking.

Effect of IRAK-M on Airway Inflammation Induced by Cigarette Smoking.
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IRAK-M 对吸烟引起的气道炎症的影响

DOI:
10.1155/2017/6506953
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发表时间:
2017
影响因子:
4.6
通讯作者:
Gao J
Gao J
中科院分区:
医学3区
文献类型:
--
作者:
Gong H;Liu T;Chen W;Zhou W;Gao J

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背景IRAK-M是一种负性调节Toll样受体的蛋白,在多种疾病中表现出双重特性。我们研究了IRAK-M缺乏对小鼠模型在急性或亚急性条件下吸烟(CS-)诱导的气道炎症的影响。方法采用多种细胞和分子生物学技术,检测IRAK-M基因敲除(KO)和野生型(WT)小鼠在CS暴露3天和7周后的差异。结果在3天CS暴露下,IRAK-M KO和WT小鼠之间的气道炎症相当。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Th 17细胞的百分比和促炎细胞因子的浓度显著升高,肺树突状细胞(DC)或巨噬细胞共刺激分子CD 40和CD 86的表达显著升高。相反,7周CS暴露的IRAK-M KO小鼠表现出显著减弱的气道炎症,肺中促炎细胞因子的浓度显著降低,TcB的百分比显著增加,肺DC或巨噬细胞的CD 11b和CD 86表达降低。结论IRAK-M在CS诱导的气道炎症中具有独特的作用,并影响DC和巨噬细胞Treg/Th 17平衡及共刺激分子的表达,其作用依赖于刺激的时间和强度。
Background 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. Methods 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. Results 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. Conclusions 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.
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