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

Abstract

macrophages 5,6 . Alveolar macrophages (AM) play an indispensable role in the occurrence and development of COPD, and, at the same time, it can affect the structure of lung tissue through the initiation and degeneration of inflammation 7 .Mutative exogenous stimuli and pathological processes can change the phenotypes and functional characteristics of alveolar macrophages 8 . Since a large number of M1-type macrophage-related cytokines, such as TNF-α and IL-8, are found in bronchoalveolar lavage fluid (BAL), pulmonary macrophages from patients with COPD have been recommended to display M1 phenotypes 9 . In addition, TNF-α has been ABSTRACT INTRODUCTION In 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. METHODS We 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. RESULTS The 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. CONCLUSIONS We 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.

Exosomes Derived from microRNA-21 Overexpressing Neural Progenitor Cells Prevent Hearing Loss from Ischemia-Reperfusion Injury in Mice via Inhibiting the Inflammatory Process in the Cochlea

“…miR-21 can modulate the polarization of macrophages into an M2-like phenotype, , and miR-21 plasmid direct transfection could result in significant upregulation of inflammatory cytokines to promote the inflammatory phenotype . On the other hand, genetic deficiency of miR-21 may promote the polarization of macrophages toward M1 macrophages .…”

Protective effects of budesonide on LPS‑induced podocyte injury by modulating macrophage M1/M2 polarization: Evidence from in vitro and in silico studies

“…Macrophages are the most abundant immune cells in the lung (~70% of all immune cells) and they serve important roles in environmental allergen-induced airway inflammation in asthma. Activated macrophages commonly exist in two distinct subtypes: the protective roles of M2 macrophages and pathogenic roles of M1 macrophages have been discussed in a number of lung diseases, including asthma and COPD ( 34 , 35 ). Macrophage polarization to the M1 subtype is an important specifying feature of inflammation, which is involved in the progression of pulmonary inflammation and secretion of TNF-α ( 36 ).…”

“…To date, some research on airway inflammation, M1/M2 macrophage polarization and secretion of TNF-α have been reported in asthmatic and COPD animal models and in vitro ( 37-39 ). Some in vitro M1/M2 research is also performed in human primary monocyte-derived macrophages ( 40 ) and RAW264.7 cells ( 35 , 41 ). According to the current in vivo and in vitro M1/M2 research in lung diseases, iNOS ( 36 ) and TNF-α ( 36 , 39 , 40 ) are important indicators of the M1 subtype and Arg-1( 36 ) and CD206 ( 35 , 36 ) are indicators of the M2 subtype.…”

“…Some in vitro M1/M2 research is also performed in human primary monocyte-derived macrophages ( 40 ) and RAW264.7 cells ( 35 , 41 ). According to the current in vivo and in vitro M1/M2 research in lung diseases, iNOS ( 36 ) and TNF-α ( 36 , 39 , 40 ) are important indicators of the M1 subtype and Arg-1( 36 ) and CD206 ( 35 , 36 ) are indicators of the M2 subtype.…”

Potential Pathogenic Impact of Cow’s Milk Consumption and Bovine Milk-Derived Exosomal MicroRNAs in Diffuse Large B-Cell Lymphoma

“…Tumor-associated macrophages (TAMs) comprise an important part of the TME, are predominantly M2-polarized, and play a key role in DLBCL progression [ 469 , 470 , 471 , 472 ]. Compelling evidence in various cancer entities underlines the impact of miR-21-5p in driving M2 polarization of macrophages and TAMs [ 473 , 474 , 475 , 476 ], whereas inhibition or depletion of miR-21 reversed M2 polarization back to the M1 phenotype [ 477 , 478 , 479 ]. Remarkably, miR-21 depletion in macrophages promotes tumoricidal polarization and enhances PD-1 immunotherapy [ 477 ].…”