Exposure to ephedrine attenuates Th1/Th2 imbalance underlying OVA-induced asthma through airway epithelial cell-derived exosomal lnc-TRPM2-AS

Background and objective: Despite the management of cough-variant asthma can be achieved via different anti-inflammatory medications, such as ephedrine, the underlying mechanism remains to be elucidated. Recent studies have also shown that airway epithelial cell (AEC)-derived exosomes contain diverse components, such as mRNA, miRNAs and lncRNAs, which affect the occurrence and development of airway inflammation. This study aims to identify the role of AEC-derived exosomes on ephedrine-mediated cough-variant asthma. Methods: A mouse asthma model was established. The airway resistance and serum inflammatory cells were examined. RT-qPCR, western blot and ELISA were employed to validate the expression of gene and protein expressions. Exosomes were isolated and characterized. RIP and RNA pull-down assay were used to detect the interaction of hnRNPA2B1 and lnc-TRPM2-AS1. Results: The inflammatory response, airway resistance and Th1/Th2 imbalance in the ovalbumin (OVA)-challenged mouse asthma model were attenuated by ephedrine. The exosomes derived from OVA-treated AECs expressed higher expression of lnc-TRPM2-AS1, which was reversed by ephedrine treatment. The exosomal lnc-TRPM2-AS1 played a critical role in mediating the Th1/Th2 imbalance of CD4 ⁺ T cells. The packaging of lnc-TRPM2-AS1 into exosomes was mediated by hnRNPA2B1. Conclusion: This present study revealed a new mechanism of ephedrine treatment that restored the OVA-triggered imbalance of CD4 ⁺ T cells by inhibiting AEC-derived exosomal lnc-TRPM2-AS1. This study may provide a theoretical basis for the treatment of asthma by exposure to ephedrine.