The Significance of Hypothiocyanite Production via the Pendrin/DUOX/Peroxidase Pathway in the Pathogenesis of Asthma

Figure 1

Schematic model of OSCN⁻ production via the pendrin/DUOX/peroxidase pathway in airway epithelial cells (modified from [9]). In airway epithelial cells, SCN⁻ is actively transported into pulmonary lumens via NIS/SLC5A5 at the basal side and via several anion transporters including CFTR and pendrin/SLC26A4 at the apical side. SCN⁻ together with H₂O₂ generated by Duox1 and Duox2 is catalyzed by peroxidases into OSCN⁻. Three peroxidases including MPO, EPX, and LPO are involved in this reaction. A low dose of OSCN⁻ activates NF-κB via PKA, whereas a high dose of OSCN⁻ causes necrosis followed by release of IL-33 in airway epithelial cells. It is of note that if peroxidases are inhibited, it would protect airway epithelial cells against inflammation.