Altered polarization of PAR-2 signaling during airway epithelial remodeling

Ryan M. Carey; Jenna R. Freund; Benjamin M. Hariri; Nithin D. Adappa; James N. Palmer; Robert J. Lee

We hypothesized basolateral polarization of PAR-2 may limit its activation except during times of epithelial barrier breakdown during infection or inflammation. Alteration of epithelial polarization or cell type composition occurs in obstructive airway diseases such as asthma and COPD. 9, 10 Loss of airway cilia may occur with viral or bacterial infection, [11] [12] [13] [14] type-2 inflammationdriven remodeling, 15 or smoking. 16, 17 Squamous metaplasia occurs after bacterial infection, particularly in cystic fibrosis-related CRS, 18 and is frequently reported in CRS patient tissue samples. 19, 20 Much of the literature on airway remodeling focuses on barrier dysfunction, but airway cells in vitro can maintain tight junctions and barrier function despite substantial morphological changes, including loss of cilia. 12 Less is known about how signaling is altered before large scale barrier breakdown in severe disease. We hypothesized that loss of epithelial polarization may affect PAR-2 signaling independently of barrier disruption, perhaps sensitizing cells to protease allergens.