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.
Keywords: CRSwNP; HNE; MUC5AC; TRAF6; autophagy.