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MiR-135b Alleviates Airway Inflammation in Asthmatic Children and Experimental Mice with Asthma via Regulating CXCL12
Immunological Investigations ( IF 2.8 ) Pub Date : 2020-11-18 , DOI: 10.1080/08820139.2020.1841221
Ying Liu 1 , Shi-Guang Huo 2 , Ling Xu 3 , Yuan-Yuan Che 1 , Shi-Yuan Jiang 4 , Li Zhu 1 , Min Zhao 5 , Yue-Chun Teng 6
Affiliation  

ABSTRACT

Objective

To clarify the possible influence of miR-135b on CXCL12 and airway inflammation in children and experimental mice with asthma.

Methods

The expressions of miR-135b and CXCL12 were detected using quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) in the serum of asthmatic children. Besides, the experimental asthmatic mice were established by aerosol inhalation of ovalbumin (OVA) followed by the treatment with agomiR-135b and antagomir-135b. Pathological changes of lung tissues were observed via HE staining and PAS staining. Besides, the airway hyperresponsiveness of mice was elevated and bronchoalveolar lavage fluid (BALF) was isolated for cell categorization and counting. The inflammatory cytokines in BALF were determined by enzyme-linked immunosorbent assay (ELISA), and the infiltration of Th17 cells in lung tissues was measured using flow cytometry.

Results

MiR-135b was downregulated and CXCL12 was upregulated in asthmatic children and mice. Overexpression of miR-135b may down-regulate CXCL12 expression in the lung of OVA mice, resulting in significant decreases in inflammatory infiltration, hyperplasia of goblet cell, airway hyperresponsiveness, cell quantity, as well as the quantity of eosinophilic granulocytes, neutrophils and lymphocytes in BALF. Also, the levels of inflammatory cytokines (IL-4, IL-5, IL-13 and IL-17) and the ratio of Th17 cells and IL-17 levels in lung tissues were decreased. However, miR-135b downregulation reversed these changes in OVA mice.

Conclusion

MiR-135b may inhibit immune responses of Th17 cells to alleviate airway inflammation and hyperresponsiveness in asthma possibly by targeting CXCL12, showing the potential value in asthma treatment.



中文翻译:

MiR-135b 通过调节 CXCL12 减轻哮喘儿童和哮喘实验小鼠的气道炎症

摘要

客观的

阐明 miR-135b 对患有哮喘的儿童和实验小鼠的 CXCL12 和气道炎症的可能影响。

方法

采用定量逆转录聚合酶链反应(qRT-PCR)检测哮喘患儿血清中miR-135b和CXCL12的表达。此外,通过雾化吸入卵清蛋白(OVA),然后用agomiR-135b和antagomir-135b处理来建立实验性哮喘小鼠。HE染色和PAS染色观察肺组织病理变化。此外,小鼠气道高反应性升高,分离支气管肺泡灌洗液(BALF)进行细胞分类和计数。采用酶联免疫吸附法(ELISA)检测BALF中炎性细胞因子,流式细胞仪检测肺组织Th17细胞浸润情况。

结果

在哮喘儿童和小鼠中,MiR-135b 下调,CXCL12 上调。miR-135b过表达可下调OVA小鼠肺中CXCL12的表达,导致炎症浸润、杯状细胞增生、气道高反应性、细胞数量以及嗜酸性粒细胞、中性粒细胞和淋巴细胞数量显着减少。巴尔夫。此外,肺组织中炎性细胞因子(IL-4、IL-5、IL-13和IL-17)的水平以及Th17细胞和IL-17水平的比例降低。然而,miR-135b 下调逆转了 OVA 小鼠的这些变化。

结论

MiR-135b 可能通过靶向 CXCL12 抑制 Th17 细胞的免疫反应,从而减轻哮喘的气道炎症和高反应性,显示出治疗哮喘的潜在价值。

更新日期:2020-11-18
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