Priority Research Centre for Asthma and Respiratory Disease, Department of Microbiology and Immunology, School of Pharmacy and Biomedical Sciences, Faculty of Health and Hunter Medical Research Institute, University of Newcastle, Newcastle, NSW, Australia.
Clin Exp Allergy. 2013 Sep;43(9):981-99. doi: 10.1111/cea.12170.
Chronic inflammatory diseases (e.g. asthma and chronic obstructive pulmonary disease)are leading causes of morbidity and mortality world-wide and effective treatments are limited. These disorders can often be attributed to abnormal immune responses to environmental stimuli and infections. Mechanisms leading to inflammation are complex,resulting from interactions of structural cells and activation of both the adaptive and innate arms of the immune system. The activation of structural and immune cells involves both temporary and permanent changes in gene expression in these cells, which underpin chronic inflammation and tissue dysfunction. miRNAs are small non-coding RNAs increasingly being recognized to play important roles in the post-transcriptional regulation of gene expression in mammalian cells by regulating translation. Individual miRNA scan exert their effects by directly inhibiting the translation or stability of multiple mRNAs simultaneously. Thus, the expression or blockade of function of a single miRNA (miR) can result in pronounced alterations in protein expression within a given cell. Dysregulation of miRNA expression may subsequently alter cellular function, and in certain situations predispose to disease. Our current understanding of the role of miRNA in the regulation of inflammatory disease (e.g. allergic diseases) remains limited. In this review, we provide an overview of the current understanding of miRNA biogenesis and function, the roles miRNA play in the regulation of immune cell function and their potential contribution to inflammatory diseases. We also highlight strategies to alter miRNA function for experimental or therapeutic gain, and discuss the potential utility and limitations of targeting these molecules as anti-inflammatory strategies.
慢性炎症性疾病（如哮喘和慢性阻塞性肺疾病）是全球发病率和死亡率的主要原因，有效的治疗方法有限。这些疾病通常可归因于对环境刺激和感染的异常免疫反应。导致炎症的机制很复杂，是结构细胞相互作用和适应性及固有免疫系统激活的结果。结构细胞和免疫细胞的激活既涉及这些细胞中基因表达的暂时变化，也涉及永久性变化，这是慢性炎症和组织功能障碍的基础。miRNA 是小的非编码 RNA，越来越多地被认为通过调节翻译在哺乳动物细胞中基因表达的转录后调控中发挥重要作用。单个 miRNA 扫描通过直接抑制多个 mRNA 的翻译或稳定性同时发挥其作用。因此，单个 miRNA（miR）的表达或功能阻断可导致给定细胞内蛋白质表达的明显改变。miRNA 表达的失调随后可能改变细胞功能，并在某些情况下易患疾病。我们目前对 miRNA 在炎症性疾病（如过敏性疾病）调节中的作用的认识仍然有限。在这篇综述中，我们概述了 miRNA 生物发生和功能的当前认识、miRNA 在免疫细胞功能调节中的作用及其对炎症性疾病的潜在贡献。我们还强调了改变 miRNA 功能的策略，以获得实验或治疗增益，并讨论了将这些分子作为抗炎策略的潜在效用和局限性。
