The inhibitor miR-21 regulates macrophage polarization in an experimental model of chronic obstructive pulmonary disease.

Abstract

INTRODUCTIONIn chronic obstructive pulmonary disease (COPD), macrophages play an indispensable role. In the lung tissues of COPD patients and smokers, macrophages can be observed to polarize towards M2 phenotype. The molecular mechanism of this process is unclear, and it has not been fully elucidated in COPD.METHODSWe bought laboratory animals [C57BL/6 and miR-21–/– C57BL/6(F1)] from the Jackson Laboratory. The model of COPD mice was established by cigarette smoke (CS) exposure combined with intraperitoneal injection of cigarette smoke extract (CSE). RT-PCR detected the expression levels of inflammatory factors and markers associated with M1 and M2 macrophages. The ratio of M2 macrophages to M1 macrophages was detected by immunohistochemical staining.RESULTSThe level of miR-21 was increased in RAW264.7 cells intervened by CSE and in lung tissue and bone marrow-derived macrophages (BMDMs) from COPD mice. CSE can gradually over time increase the level of miR-21. The proportion of M2 macrophages to M1 macrophages had a positive correlation with miR-21. Knockdowning miR-21 can reduce lung tissue damage. CSE also increased the levels of related inflammatory factors and markers associated with M2 macrophages, and an miR-21 inhibitor can reverse this conversion.CONCLUSIONSWe confirmed that CSE can lead to macrophage transformation to the M2 phenotype and an increase in the expression level of miR-21. Knockdown of the miR-21 gene could inhibit the transformation of macrophages to the M2 phenotype in COPD.