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

• Published in: American journal of rhinology & allergy Vol. 36; no. 6; p. 816
• Main Authors: Zhang, Ying, Qi, Jing, Yan, Danqing, Deng, Yangquan, Zhang, Jian, Luo, Qing
• Format: Journal Article
• Language: English
• Published: United States 01.11.2022
• Subjects: Autophagy; Beclin-1 - metabolism; Chronic Disease; Humans; Leukocyte Elastase - metabolism; Mucin 5AC - genetics; Mucin 5AC - metabolism; Nasal Polyps - metabolism; Rhinitis - metabolism; RNA, Messenger; Sinusitis - metabolism; TNF Receptor-Associated Factor 6 - genetics; TNF Receptor-Associated Factor 6 - metabolism; CRSwNP; autophagy; TRAF6; HNE; MUC5AC
• ISSN: 1945-8932
• DOI: 10.1177/19458924221116939

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. To investigate the role of TRAF6 in the human neutrophil elastase (HNE)-induced autophagy and mucin MUC5AC over-expression in CRSwNP. 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. 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. HNE promotes autophagy through TRAF6, resulting in hyperexpression of MUC5AC in CRSwNP.