ADAM28 promotes epithelial mesenchymal transition and impairs tight junctions in non-eosinophilic chronic rhinosinusitis with nasal polyps by inducing M1 polarization of macrophages.

BACKGROUND

Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by tight junction dysfunction associated with epithelial-mesenchymal transition (EMT) processing. ADAM28 participates in the pathogenic process of inflammatory airway diseases.

METHODS

The effects of ADAM28 knockdown on the expression levels of the M1-type macrophage markers were examined using M1-type macrophage polarization model established with the THP1 cells. An inflammation model was established by collecting cell supernatants from M1-polarized macrophages with stable ADAM28 knockdown to stimulate HNEPC and primary nasal mucosal epithelial cells (pHNECs).The expression levels of EMT markers and tight junction proteins were detected.

RESULTS

ADAM28 was highly expressed in non-eosinophilic CRSwNP (NE-CRSwNP) and correlated with NE-CRSwNP clinical scores. Immunofluorescence assay demonstrated that the number of ADAM28-positive macrophages significantly increased in the NE-CRSwNP group compared with the control group. In addition, ADAM28 levels were significantly elevated in M1-type macrophages. ADAM28 knockdown significantly reduced the expression levels of M1-type macrophage polarization markers in M1 macrophages. Furthermore, ADAM28 knockdown elevated the expression of EMT marker E-cadherin and decreased the expression of α-SMA in HNEPC and pHNECs. Additionally, ADAM28 knockdown increased the expression levels of tight junction proteins in pHNECs cultured at an air-liquid interface.

CONCLUSION

ADAM28 is markedly elevated in NE-CRSwNP and is correlated with the clinical scores of NE-CRSwNP. ADAM28 induces the M1-type polarization of macrophages. ADAM28 promotes EMT and impairs tight junctions of nasal epithelia by inducing M1-type polarization of macrophages.