The Role Of Autophagy In The Overexpression Of MUC5AC In Chronic Rhinosinusitis

Objective:Investigated the role of autophagy in pathogenic mucin(MUC)5AC production during chronic rhinosinusitis(CRS).Methods:1.The expression of human neutrophil elastase(HNE)and the autophagic proteins microtubule-associated protein 1 light chain(LC)3B-II,c-Jun N-terminal kinase(JNK),c-Jun,and MUC5 AC were analyzed in the sinonasal mucosa and human nasal epithelial cells(HNECs)using immunohistochemistry,enzyme-linked immunosorbent assay(ELISA),and quantitative real-time polymerase chain reaction(qRT-PCR).2.Autophagic vacuoles were studied using transmission electron microscopy(TEM).Primary HNECs were treated with HNE,bafilomycin A1,and SP600125.3.Cultured primary HNECs were transfected with small interfering RNAs(siRNAs)to target Beclin-1(BECN1;BECN1-siRNA),autophagy-related gene 5(Atg5;Atg5-siRNA),and c-Jun(c-Jun-siRNA).Cultured cells were analyzed using western blotting,qRT-PCR,and ELISA.Results:1.In CRS patients,both with and without nasal polyps,the expression levels of HNE,LC3 B,JNK,c-Jun,and MUC5 AC were upregulated.2.Bafilomycin A1 upregulated LC3B-II expression and inhibited MUC secretion in HNE-treated normal primary HNECs.Autophagosomes were observed in HNE-treated primary HNECs using TEM.3.HNE-induced secretion of MUC5 AC was suppressed in normal primary HNECs by BECN1-siRNA,Atg5-siRNA,c-Jun-siRNA,and SP600125.Conclusions:In HNE-induced CRS,autophagy reduces the secretion of MUC5 AC by inhibiting the phosphorylation of JNK and c-Jun.