Conclusion
Using a newly developed, stable experimental model of nasal hypersecretion in mice, we showed that TAPI-2 or AG1478 inhibited HNE-induced MUC5AC production. This suggests that MUC5AC mucin expression in vivo is mediated by a cascade involving the HNE-TACE-EGFR signalling pathway.
Results
Compared to the control group, HE-stained tissues from the HNE group showed an irregular epithelium as well as goblet cell and submucosal glandular hyperplasia. In the nasal mucosa, strongly positive fuchsia granules were seen in PAS staining and significant increases in TACE, EGFR, MUC5AC mRNA, and protein expression were detected (p < 0.01). The HNE + TAPI-2 and HNE + AG1478 groups had significantly less goblet cell and submucosal gland hyperplasia as well as weaker PAS staining. Compared to mice treated with HNE alone, in HNE + TAPI-2-treated mice, the levels of TACE, EGFR, and MUC5AC mRNA and protein as well as p-EGFR protein were significantly reduced (p < 0.01). In HNE + AG1478-treated mice, EGFR and MUC5AC mRNA and protein levels and p-EGFR protein expression were reduced significantly (p < 0.01), but the difference in TACE mRNA and protein expression between the HNE + AG1478 and HNE groups was not significant (p > 0.05).