Oncostatin M promotes epithelial barrier dysfunction and is elevated in eosinophilic mucosal disease (HYP7P.255)

Abstract

Abstract Epithelial barrier dysfunction is thought to play a role in many mucosal diseases including asthma, chronic rhinosinusitis (CRS), and eosinophilic esophagitis (EoE). Oncostatin M (OSM), was elevated in both mRNA (28.3 fold, p<.01, n=12) and protein (4.4 fold, p<.05, n=12-19) in the nasal polyps of CRS patients compared to control tissue. OSM protein was also elevated in bronchoalveolar lavage (BAL) of allergic asthma (AA) patients following segmental allergen challenge (SAC) vs. saline challenge (14 fold, p<.0001). Additionally, OSM mRNA was elevated in esophageal biopsies of EoE patients vs. controls, (3 fold, p<.01). OSM stimulation of differentiated airway epithelium induced barrier dysfunction, as measured by decreased transepithelial electrical resistance (63% reduction, p<.0001, n=11) and increased permeability to 10kD dextran (2.45 fold, p<.05, n=5). Staining for the tight junction protein, occludin showed that OSM stimulation of differentiated airway epithelium impaired the organization of the tight junctions compared to unstimulated controls (n=5). Levels of OSM protein in tissue lysates from CRS and controls correlated with levels of α2-macroglobulin, a marker of epithelial leak, in matched nasal secretions (r=.5055, p<.01). Additionally, OSM in the BAL following SAC in AA patients correlated with serum albumin, another marker of epithelial leak (r=.8062, p<.001). These results suggest that OSM may play a role in epithelial barrier dysfunction in mucosal disease.