TRIM47 promotes HDM-induced bronchial epithelial pyroptosis by regulating NEMO ubiquitination to activate NF-κB/NLRP3 signaling.

ABSTRACT

Asthma is an inflammatory disease. Airway epithelial cell pyroptosis and cytokine secretion promote asthma progression. Tripartite motif 47 (TRIM47) belongs to the E3 ubiquitin ligase family and is associated with apoptosis and inflammation in a range of diseases. However, the role of TRIM47 in asthma has not been explored. In this study, the human bronchial epithelial cell line BEAS-2B was treated with house dust mite (HDM) and TRIM47 expression was detected by RT-qPCR and Western blot. After transfection with TRIM47 interfering and overexpressing plasmids, the synthesis and secretion of cytokines, as well as pyroptosis-related indicators, were examined. Nuclear factor kappa-B (NF-κB) pathway proteins and nod-like receptor protein 3 (NLRP3) inflammasome were measured to explore the mechanism of TRIM47 action. In addition, the effect of TRIM47 on the level of NF-κB essential modulator (NEMO) ubiquitination was detected by an immunoprecipitation assay. The results showed that TRIM47 was upregulated in HDM-induced BEAS-2B cells and that TRIM47 mediated HDM-induced BEAS-2B cell pyroptosis and cytokine secretion. Mechanistically, TRIM47 promoted the K63-linked ubiquitination of NEMO and facilitated NF-κB/NLRP3 pathway activation. In conclusion, TRIM47 may promote cytokine secretion mediating inflammation and pyroptosis in bronchial epithelial cells by activating the NF-κB/NLRP3 pathway. Therefore, TRIM47 may be a potential therapeutic target for HDM-induced asthma.