Antagonism of mmu-mir-106a attenuates asthma features in allergic murine model.
Antagonism of mmu-mir-106a attenuates asthma features in allergic murine model.
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DOI：
10.1152/japplphysiol.00001.2012
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发表时间：
2012-08
影响因子：
3.3
通讯作者：
Amit Sharma;Manish Kumar;T. Ahmad;U. Mabalirajan;J. Aich;A. Agrawal;B. Ghosh
中科院分区：
文献类型：
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作者：
Amit Sharma;Manish Kumar;T. Ahmad;U. Mabalirajan;J. Aich;A. Agrawal;B. Ghosh
MicroRNA (miR) 调节健康和疾病的免疫通路，并且许多 miR 已被证明在哮喘小鼠模型中发生了改变。白细胞介素 10 (IL-10) 是一种抗炎细胞因子，已被证明在包括哮喘在内的许多炎症性疾病中存在缺陷。我们最近证明 miR-106a 以转录后方式抑制 IL-10。在这项研究中，我们研究了抑制 mmu-miR106a 在哮喘病中的作用，以发现其作为治疗靶点的可能作用。我们对小鼠巨噬细胞 RAW264.7 进行的体外实验表明，mmu-miR-106a 可能会降低 IL-10，同时增加促炎细胞因子。此外，对初始小鼠施用mmu-miR-106a以剂量依赖性方式降低肺部IL-10水平，而不改变肺部组织学。最有趣的是，在已确定的过敏性气道炎症中敲低 mmu-miR-106a 可显着缓解哮喘的大部分特征，如气道高反应性、气道炎症、Th2 反应增强、杯状细胞化生和上皮下纤维化，同时肺部 IL-10 水平增加。这是第一个体内证据，证明 miRNA 介导的 IL-10 调节具有逆转既定哮喘病的潜力。
MicroRNAs (miRs) regulate immunological pathways in health and disease, and a number of miRs have been shown to be altered in mouse models of asthma. The secretion of interleukin-10 (IL-10), an anti-inflammatory cytokine, has been shown to be defective in many inflammatory diseases including asthma. We recently demonstrated that miR-106a inhibits IL-10 in a post-transcriptional manner. In this study, we investigated the effect of inhibition of mmu-miR106a in asthmatic condition to find its possible role as a therapeutic target. Our in vitro experiments with mouse macrophage, RAW264.7, revealed that mmu-miR-106a potentially decreased IL-10 along with increase in proinflammatory cytokine. Furthermore, administration of mmu-miR-106a to naive mice reduced IL-10 levels in lungs in a dose-dependent manner without altering lung histology. Most interestingly, knockdown of mmu-miR-106a in an established allergic airway inflammation has significantly alleviated most of the features of asthma such as airway hyperresponsiveness, airway inflammation, increased Th2 response, goblet cell metaplasia, and subepithelial fibrosis along with increase in IL-10 levels in lung. This represents the first in vivo proof of a miRNA-mediated regulation of IL-10 with a potential to reverse an established asthmatic condition.