A novel inhibitory role of microRNA‐224 in particulate matter 2.5‐induced asthmatic mice by inhibiting TLR2

Epidemiological studies have shown that elevated concentrations of particulate matter 2.5 (PM2.5) correlate with increased incidence of asthma. Studies have highlighted the implication of microRNAs (miRNAs) in asthmatic response. Here, the objective of this study is to explore the effect of miR‐224 on PM2.5‐induced asthmatic mice. Ovalbumin (OVA) was utilized to establish asthmatic mouse models, which were then exposed to PM2.5, followed by miR‐224 expression detection. Next, lesions and collagen deposition area in lung tissue, ratio Treg/Th17, the expression of TLR4 and MYD88, inflammation, eosinophils (EOS) and airway remodelling were evaluated in OVA mice after injection with miR‐224 agomir. Following isolation of mouse primary bronchial epithelial cells, miR‐224 mimic and TLR2/TLR4 inhibitor were introduced to assess inflammation and the expression of TGF‐β, MMP9, TIMP‐1, Foxp3, RORγt, TLR2, TLR4 and MYD88. After exposure to PM2.5, lesions and collagen deposition were promoted in lung tissues, inflammation and EOS were increased in bronchoalveolar lavage fluid (BALF), and airway remodelling was enhanced in OVA mice. miR‐224 was down‐regulated, whereas TLR2/TLR4/MYD88 was up‐regulated in OVA mice after treatment with PM2.5, accompanied by Treg/Th17 immune imbalance. Of note, bioinformatic prediction and dual luciferase reporter gene assay confirmed that TLR2 was a target gene of miR‐224. Overexpressed miR‐224 reduced expression of TGF‐β, MMP9, TIMP‐1 and RORγt and inflammation but increased Foxp3 expression in bronchial epithelial cells through down‐regulating TLR2. In summary, overexpressed miR‐224 suppressed airway epithelial cell inflammation and airway remodelling in PM2.5‐induced asthmatic mice through decreasing TLR2 expression.