Angiotensin-II (Ang-II) receptor plays a role in allergic airway inflammation; however, the underlying mechanism and role of macrophages need better understanding. In the present study, angiotensin-II infusion (1 μg/kg/min) in ovalbumin-induced airway inflammation mice model significantly decreased immune cell infiltration, goblet cell hyperplasia, and eosinophil numbers in lungs. Ang-II infusion increased M1 and decreased M2 macrophage population in bronchoalveolar lavage fluid and respective macrophage markers in lung macrophages. Similarly, in vitro Ang-II treatment in murine bone marrow-derived macrophages (BMDMs) induced M1 and reduced M2 macrophage phenotype with enhanced bactericidal activity. Mechanistically, Ang-II inhibits Let-7c and miR-99a expression in BMDMs and in vivo as well. Lentiviral overexpression of Let-7c and miR-99a miRNAs in BMDMs abrogated Ang-II-induced M1 phenotype activation and promoted M2 phenotype, which is governed by targeting TNFα by miR-99a. In lung macrophages, ovalbumin-induced TNFα inhibition was rescued after Ang-II treatment. In BMDMs, knockdown of TNFα abrogated Ang-II-induced M2 to M1 macrophage phenotype switch and associated bactericidal activity. Ang-II affects mature miRNA formation by enhancing Lin28B levels in macrophages in vivo and in vitro. Furthermore, Lin28B knockdown prevented Ang-II-mediated inhibition of mature Let-7c/miR-99a miRNA formation, M2 to M1 macrophage phenotype switch, and increased bactericidal activity. Therefore, present study suggests a role of Lin28B in Ang-II-induced Let-7c/miR-99a miRNA formation that consequently affects TNFα production, M1 phenotype activation, and allergic airway inflammation.

Ovalbumin inhibits LIN28B expression thereby fails to inhibit premature to mature Let-7c/miR-99a miRNA formation. Mature miR-99a miRNA that inhibits TNFα consequently promotes M2 polarization and allergic airway inflammation.

While Ang-II induces Lin28B, which inhibits Let-7c/miR-99a miRNA processing and mature miRNA formation, this results in increased TNFα levels that lead to M1 polarization and allergic airway inflammation inhibition.

血管紧张素II（Ang-II）受体在过敏性气道炎症中起作用。然而，巨噬细胞的潜在机制和作用需要更好的理解。在本研究中，在卵清蛋白诱导的气道炎症小鼠模型中血管紧张素II输注（1μg/ kg / min）显着降低了免疫细胞浸润，杯状细胞增生和肺中嗜酸性粒细胞数量。Ang-II输注可增加支气管肺泡灌洗液中M1和M2巨噬细胞的数量，并减少肺巨噬细胞中相应的巨噬细胞标志物。同样，在小鼠骨髓源性巨噬细胞（BMDM）中进行的体外Ang-II治疗诱导了M1并降低了M2巨噬细胞的表型，并具有增强的杀菌活性。从机理上讲，Ang-II抑制BMDM和体内的Let-7c和miR-99a表达也一样 在BMDM中，Let-7c和miR-99a miRNA的慢病毒过度表达消除了Ang-II诱导的M1表型激活并促进了M2表型，这由miR-99a靶向TNFα控制。在肺巨噬细胞中，Ang-II治疗后挽救了卵白蛋白诱导的TNFα抑制。在BMDM中，TNFα的敲除消除了Ang-II诱导的M2至M1巨噬细胞表型转换和相关的杀菌活性。Ang-II通过增强体内和体外巨噬细胞中的Lin28B水平来影响成熟的miRNA形成。此外，Lin28B敲低阻止了Ang-II介导的成熟Let-7c / miR-99a miRNA形成抑制，M2至M1巨噬细胞表型转换以及增加的杀菌活性。因此，本研究提示Lin28B在Ang-II诱导的Let-7c / miR-99a miRNA形成中的作用，从而影响TNFα的产生，M1表型的激活和过敏性气道炎症。

卵清蛋白抑制LIN28B表达，因此不能抑制过早成熟的Let-7c / miR-99a miRNA形成。因此，抑制TNFα的成熟miR-99a miRNA会促进M2极化和过敏性气道炎症。

Ang-II诱导Lin28B抑制Let-7c / miR-99a miRNA加工并形成成熟的miRNA时，这导致TNFα水平升高，导致M1极化和过敏性气道炎症抑制。