MicroRNA‐22‐3p plays a protective role in a murine asthma model through the inhibition of the NLRP3–caspase‐1–IL‐1β axis. Issue 8 (20th May 2021)

• Record Type: Journal Article
• Authors: Guo, Shufang; Chen, Ru; Zhang, Lina; Wu, Meiqiong; Wei, Yangyang; Dai, Wenjuan; Jiang, Yi; Kong, Xiaomei
• Is Part Of: Experimental physiology. Volume 106:Issue 8(2021)
• Page Start: 1829
• Page End: 1838
• Publication Date: 2021-05-20
• Subjects: asthma -- caspase‐1 -- IL‐1β -- microRNA‐22‐3p -- NLRP3; Physiology, Experimental -- Periodicals; 571.0724
• DOI: 10.1113/EP089575
• Languages: English
• ISSNs: 0958-0670

Abstract

Abstract : New Findings: What is the central question of this study? How does miR‐22‐3p exert a protective role in asthma? What is the main finding and its importance? Upregulation of miR‐22‐3p hampered airway inflammation and release of inflammatory cytokines through blocking the activation of the NLRP3–caspase‐1–IL‐1β signalling pathway in asthma. Abstract: Asthma, a great public health burden, is triggered by inflammatory responses in the airways and these are not addressed appropriately by current therapies. This study aims to investigate the regulatory mechanism of microRNA‐22‐3p (miR‐22‐3p) on the proliferation of bronchial epithelial cells exposed to lipopolysaccharide (LPS) and expression of pro‐inflammatory cytokines in a murine asthma model challenged by ovalbumin. We first confirmed the downregulation of miR‐22‐3p in the murine asthma model and bronchial epithelial cells. miR‐22‐3p remarkably reversed the decline in bronchial epithelial cell viability, enhancement in apoptosis rate and release of inflammatory factors induced by LPS. miR‐22‐3p targeted and conversely regulated NACHT, LRR and PYD domains‐containing protein 3 (NLRP3). Overexpression of NLRP3 counteracted the inhibitory effect of miR‐22‐3p on inflammatory damage in bronchial epithelial cells through activation of caspase‐1/interleukin (IL)‐1β. In an in vivo model, overexpression of miR‐22‐3p significantly attenuated airway obstruction and tissue damage in mice. In summary, our study underscores that miR‐22‐3p serves both as a negative regulator of the NLRP3–caspase‐1–IL‐1β axis and as a protective factor against the inflammatory response, suggesting a future therapeutic role in asthma. Abstract :