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

Ping Li,Baihong Zheng,Fengjun Guo,Xuelei Zhang,Jinpeng Wang

doi:10.1111/jcmm.14940

Abstract

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.

Highlights

We found that PM2.5 could aggravate inflammatory response and airway remodelling, and induce Treg/Th17 cell imbalance via activation of the TLR2/TLR4/MYD88 pathway (Figure 6)
The present study showed that overexpression of miR-224 could inhibit the inflammation caused by PM2.5 by targeting TLR2 which suggested that miR-224 may act as an inhibitor against the development of asthma
PM2.5 could increase the secretion of several interleukins and break the immune balance of Treg/Th17 cells, which eventually exacerbated the inflammation in lung tissue of OVA mouse model

Summary

| METHODS

Asthma is a complicated condition that gets recurrent episodes of airway obstruction in which airways narrow and produce extra mucus. Th2 cell is primarily verified to control the innate or allergic inflammation by secreting interleukin 4 and 13 (IL-4 and IL-13) with the help of Treg cell.[6] Th17 cell is a new kind of T-helper cell found recently and involved in autoimmune and inflammatory diseases.[6] one study has suggested that Th17 cells can enhance inflammation in eosinophilic airway mediated by Th2-cell.[7] microbes' infection has been verified to activate Th2-cell response via recognizing TLR2, but the underlying inflammatory mechanism involving particulate matter, especially PM2.5, in airway and lung tissue is still not well characterized. We aim to investigate the role of miR-224 in the airway remodelling and Treg/Th17 cells dynamics in ovalbumin (OVA)-induced asthmatic mice affected by PM2.5. The present study proved that miR-224 was an inhibitor of asthma progression aggravated by PM2.5

| Ethics statement

D Saline

Findings

| DISCUSSION