miR-20b attenuates airway inflammation by regulating TXNIP and NLRP3 inflammasome in ovalbumin-induced asthmatic mice

Abstract

Objectives

Asthma is a chronic inflammatory disorder of the airway and is associated with pyroptosis. microRNAs (miRNAs) underlie pathogenic mechanism in asthma. This study is expected to evaluate the role of miR-20b in asthma-induced airway inflammation via regulating thioredoxin-interacting protein (TXNIP) and NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome.

Methods

The asthmatic mouse model was established via ovalbumin (OVA) induction. Expressions of miR-20b, TXNIP, and NLRP3 in lung tissues were determined. Bronchial hyperresponsiveness was appraised, cells in bronchoalveolar lavage fluid were counted and categorized, and histopathological damage was observed. Levels of inflammatory and pyroptotic cytokines were measured. The binding relationship of miR-20b and TXNIP was testified. Co-location and interaction between TXNIP and NLRP3 were detected. Mice were infected with the lentivirus packaged with pcDNA3.1-TXNIP or pcDNA3.1-NLRP3 for joint experiments to observe the pathological changes of mice.

Results

miR-20b was poorly expressed, while TXNIP and NLRP3 were highly expressed in OVA-induced mice. miR-20b overexpression attenuated airway inflammation and pyroptosis, manifested by alleviation of histopathological damage, declined numbers of total cells and inflammatory cells, lowered bronchial hyperresponsiveness, decreased levels of pro-inflammatory and pyroptotic cytokines, and increased anti-inflammatory cytokines. miR-20b targeted TXNIP and inhibited TXNIP expression, and TXNIP can bind to NLRP3 and upregulated NLRP3 expression. Upregulation of TXNIP or NLRP3 could reverse the protecting role of miR-20b overexpression in OVA-induced mice.

Conclusion

miR-20b inhibited TXNIP expression to reduce the binding of TXNIP and NLRP3, thus restricting pyroptosis and airway inflammation of asthmatic mice.

Keywords:

• Asthma
• airway inflammation
• miR-20b
• TXNIP
• NLRP3
• pyroptosis
• hematoxylin-eosin staining
• bronchoalveolar lavage fluid

Availability of data and material

The datasets analyzed during the current study are available from the corresponding author on reasonable request.

Declaration of interest

The authors declare that they have no competing interests.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.