Open AccessDepletion of microRNA-451 in response to allergen exposure accentuates asthmatic inflammation by regulating Sirtuin2
Author(s) -
Sangwoon Chung,
Yong Gyu Lee,
Manjula Karpurapu,
Joshua A. Englert,
Megan N. Ballinger,
Ian C. Davis,
Gye Young Park,
John W. Christman
Publication year - 2020
Publication title -
american journal of physiology. lung cellular and molecular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.892
H-Index - 163
eISSN - 1522-1504
pISSN - 1040-0605
DOI - 10.1152/ajplung.00457.2019
Subject(s) - inflammation , immunology , sirt2 , sirtuin , allergic inflammation , microrna , macrophage , ccl17 , population , macrophage polarization , medicine , house dust mite , allergy , biology , allergen , chemokine , gene , genetics , in vitro , environmental health , cxcl10 , acetylation
The incidence of asthma has increased from 5.5% to near 8% of the population, which is a major health concern. The hallmarks of asthma include eosinophilic airway inflammation that is associated with chronic airway remodeling. Allergic airway inflammation is characterized by a complex interplay of resident and inflammatory cells. MicroRNAs (miRNAs) are small noncoding RNAs that function as posttranscriptional modulators of gene expression. However, the role of miRNAs, specifically miR-451, in the regulation of allergic airway inflammation is unexplored. Our previous findings showed that oxidant stress regulates miR-451 gene expression in macrophages during an inflammatory process. In this paper, we examined the role of miR-451 in regulating macrophage phenotype using an experimental poly-allergenic murine model of allergic airway inflammation. We found that miR-451 contributes to the allergic induction of CCL17 in the lung and plays a key role in proasthmatic macrophage activation. Remarkably, administration of a Sirtuin 2 (Sirt2) inhibitor diminished alternate macrophage activation and markedly abrogated triple-allergen [dust mite, ragweed, Aspergillus fumigatus (DRA)]-induced lung inflammation. These data demonstrate a role for miR-451 in modulating allergic inflammation by influencing allergen-mediated macrophages phenotype.