HNE Induces the Hyperexpression of MUC5AC in Chronic Rhinosinusitis With Nasal Polyps by Activating the TRAF6/Autophagy Regulatory Axis

Background Hypersecretion of mucin 5AC (MUC5AC) is a prominent feature of chronic rhinosinusitis with nasal polyps (CRSwNP) and autophagy plays a pivotal role in this process. TNF receptor-associated factor 6 (TRAF6) functions as a signal transducer in many inflammation diseases, whereas the correlation between TRAF6 and autophagy in CRSwNP remains unclear. Objective To investigate the role of TRAF6 in the human neutrophil elastase (HNE)-induced autophagy and mucin MUC5AC over-expression in CRSwNP. Methods Tissue specimens were obtained from control subjects and patients with CRSwNP. The relationships between HNE, TRAF6, autophagy, and MUC5AC were investigated. The effect of TRAF6 on HNE-mediated autophagy and hypersecretion of MUC5AC was assessed by in-vitro culture of HNECs treated with human recombinant HNE. Results Patients with CRSwNP had more protein expression of HNE, MUC5AC, TRAF6, and light chain (LC3B), and increased levels of Beclin-1(BECN1) and autophagy-related gene 5 (ATG5) in mRNA level. Treatment of nasal epithelial cells with recombinant HNE induced the upregulation of TRAF6, autophagy, and MUC5AC. Alternatively, si-TRAF6 or autophagy inhibitor treatment mitigates the hyperexpression of MUC5AC before incubating with recombinant HNE. Conclusion HNE promotes autophagy through TRAF6, resulting in hyperexpression of MUC5AC in CRSwNP.

Automated summary

This study investigated the role of TNF receptor-associated factor 6 (TRAF6) in the human neutrophil elastase (HNE)-induced autophagy and mucin MUC5AC over-expression in chronic rhinosinusitis with nasal polyps (CRSwNP). The results showed that HNE promotes autophagy through TRAF6, resulting in hyperexpression of MUC5AC in CRSwNP.