期刊
INFLAMMATION
卷 43, 期 5, 页码 1846-1861出版社
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s10753-020-01258-1
关键词
Lin28B; Let-7c; miR-99a; TNF; angiotensin-II; M1; M2 phenotype; allergic inflammation
资金
- Council of Scientific and Industrial Research (CSIR)
- CSIR-CDRI
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 mu g/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 TNF alpha by miR-99a. In lung macrophages, ovalbumin-induced TNF alpha inhibition was rescued after Ang-II treatment. In BMDMs, knockdown of TNF alpha 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 TNF alpha production, M1 phenotype activation, and allergic airway inflammation.
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