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.
K E Y W O R D Sasthma, caspase-1, IL-1β, microRNA-22-3p, NLRP3
INTRODUCTIONMicroRNAs (miRNAs), short 18-22 nt single-stranded RNAs that play important parts in modulating protein expression and regulating cellular signalling, have been implicated in the development of chronic airway diseases, including asthma (Tan et al., 2020). The symptoms of asthma result from a chronic airway inflammatory response to a trigger, most frequently inhaled allergen(s), that induces airway hyper-