Department of Respiratory and Critical Care Medicine, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan, Hubei, 430071, People's Republic of China.
National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China.
Respir Res. 2020 May 18;21(1):116. doi: 10.1186/s12931-020-01374-4.
Neutrophilic subtype asthma occurs in approximately 15-25% of the asthma cases and is associated with severe airflow obstruction, corticosteroid resistance. MicroRNA plays a vital role in regulating many immune processes, but how miRNA circuits coordinate airway inflammation during neutrophilic asthma is unclear.
To investigate the molecular mechanism of miR-223 in regulation of neutrophilic airway inflammation, miR-223 knockout mice were used to the OVA/CFA-induced neutrophilic asthma or treated with NLRP3 inhibitor and IL-1β receptor antagonist. Based on the results obtained, wide-type mice were subsequently treated with miR-223 agomirs or negative control agomirs, and the effects on airway inflammation were assessed using morphometric techniques, quantitative RT-PCR, western blot, ELISA and other molecular approaches.
The expression of miR-223 was upregulated in lung tissues of experimental mice model. Furthermore, miR-223 mice led to aggravated neutrophilic airway inflammation with heightened histopathological, inflammatory cells and cytokines readouts. Moreover, miR-223 mice also presented with enhanced NLRP3 inflammasome level with elevated IL-1β. Blocking NLRP3 or IL-1β diminished this phenotype. Finally, overexpression of miR-223 via treatment with miR-223 agomirs attenuated airway inflammation, NLRP3 levels and IL-1β release.
The findings of this study revealed a crucial role for miR-223 in regulating the immunoinflammatory responses by depressing the NLRP3/ IL-1β axis in neutrophilic asthma.
嗜中性粒细胞亚型哮喘约占哮喘病例的 15-25%，与严重气流阻塞、皮质激素抵抗有关。miRNA 在调节许多免疫过程中起着至关重要的作用，但 miRNA 回路如何在嗜中性粒细胞性哮喘期间协调气道炎症尚不清楚。
为了研究 miR-223 在调节嗜中性粒细胞性气道炎症中的分子机制，使用 miR-223 敲除小鼠进行 OVA/CFA 诱导的嗜中性粒细胞性哮喘或用 NLRP3 抑制剂和 IL-1β 受体拮抗剂治疗。根据获得的结果，随后用 miR-223 agomirs 或阴性对照 agomirs 处理野生型小鼠，并通过形态计量技术、定量 RT-PCR、western blot、ELISA 和其他分子方法评估对气道炎症的影响。
miR-223 在实验小鼠模型的肺组织中表达上调。此外，miR-223 小鼠导致嗜中性粒细胞性气道炎症加重，组织病理学、炎症细胞和细胞因子读数升高。此外，miR-223 小鼠还表现出增强的 NLRP3 炎性小体水平，IL-1β 升高。阻断 NLRP3 或 IL-1β 减弱了这种表型。最后，通过用 miR-223 agomirs 处理过表达 miR-223 可减轻气道炎症、NLRP3 水平和 IL-1β 释放。
这项研究的结果表明，miR-223 通过抑制嗜中性粒细胞性哮喘中 NLRP3/IL-1β 轴在调节免疫炎症反应中起着关键作用。
