Pathophysiology of nasal polyposis: The role of desmosomal junctions

Background: Molly mucosal inflammatory conditions are associated with alterations in epithelial intercellular junctions and barrier function; however, little is known about the role of intercellular junctions in inflammatory diseases of the upper airways. In this study, We examined nasal polyps for altered intercellular junctions and protein expression. Methods: Biopsy specimens of nasal polyps and normal tissue were obtained intraoperatively from 11 patients and 6 controls. Tissue was analyzed for expression of intercellular junctional proteins by immunofluorescence. In parallel, cultured human bronchial epithelial (HBE) cells were treated with tumor necrosis factor (TNF) alpha, interferon (IFN) gamma, and IL-13 to simulate inflammatory conditions followed by assessment for changes in junctional proteins by immunofluorescence and Western blot, Results: Of the intercellular junctional proteins analyzed, including proteins comprising fight and adherens junctions, the only alterations observed were in desmosomal proteins in nasal polyp epithelium compared With normal controls. Specifically, expression of desmosomal proteins DSG(2) and DSG(3) were significantly decreased in polyps versus controls (0.53 pixel/mu m(2) versus 1.09 pixel/mu m(2) [p = 0.009], and 0.29 pixel/mu m(2) versus 1.11 pixel/mu m(2) [P = 0.0078], respectively). In vitro experiments involving exposure of cultured HBE cells with inflammatory cytokines revealed that TNF-alpha treatment resulted in internalization and decreased expression of DSG(2) by immunofluorescence and Western blotting. Treatment With IFN-gamma results in increased expression of DSG(2) and evidence ofprotein cleavage by Western blot. IL-13 exposure resulted in down-regulation of DSG(2) expression and evidence of protein cleavage. Conclusion: These results indicate that nasal polyps express decreased levels of DSG(2) and DSG(3) components of desmosomal junctions. This is likely linked to the mucosal inflammatory response. Exposure of a respiratory cell line to Th1/Th2 cytokines results in similar expressional alterations in DSG(2), suggesting protein internalization and cleavage. We speculate that weakened desmosomal junctions in nasal mucosa secondary to inflammatory cytokines may contribute to the formation of nasal polyposis,