Human neutrophil elastase induces MUC5AC overexpression in chronic rhinosinusitis through tumour necrosis factor-α converting enzyme

Acta Otolaryngol. 2016 Jun;136(6):641-8. doi: 10.3109/00016489.2016.1144145. Epub 2016 Feb 16.

Abstract

Conclusion The HNE-TACE signalling pathway has an important role in the process of MUC5AC overexpression in chronic rhinosinusitis (CRS). Objectives To provide evidence of HNE-induced MUC5AC overexpression in CRS via TACE. Method HE and PAS staining were used to assess the pathological changes in sinus mucosa samples from CRS or normal control. HNE, TACE, and MUC5AC expression in the sinonasal mucosa was determined using immunohistochemistry (IHC) and real-time polymerase chain reaction (qRT-PCR). In addition, the MUC5AC and TACE expression was determined in a primary culture of human nasal mucosa epithelial cells in vitro. Results On HE staining, the main pathological feature in the sinus mucosa of CRS patients was hyperplasia of goblet cells, inflammatory cells, and submucosal glands. Mucosa from the two experimental groups also showed strong expression on PAS staining. IHC and qRT-PCR demonstrated that HNE, TACE, and MUC5AC expression was significantly higher in the CRS patients compared with control samples (p < 0.05). MUC5AC mRNA expression was higher in cells stimulated by HNE than in untreated cells (p < 0.05). MUC5AC mRNA expression was significantly reduced in cells pre-treated with the TACE inhibitor TAPI-1 prior to HNE stimulation, compared with untreated and HNE-stimulated cells (p < 0.01).

Keywords: Chronic rhinosinusitis; HNE; MUC5AC; Mucin; TACE; hyperplasia; nasal goblet cells; nasal secretions; pathogenesis; signal pathway.

MeSH terms

  • ADAM17 Protein / metabolism*
  • Adult
  • Aged
  • Case-Control Studies
  • Chronic Disease
  • Female
  • Humans
  • Leukocyte Elastase / metabolism*
  • Male
  • Maxillary Sinus / enzymology
  • Middle Aged
  • Mucin 5AC / metabolism*
  • Nasal Mucosa / enzymology*
  • Nose Diseases / enzymology*
  • Young Adult

Substances

  • MUC5AC protein, human
  • Mucin 5AC
  • Leukocyte Elastase
  • ADAM17 Protein
  • ADAM17 protein, human