Pathophysiology of nasal polyposis: the role of desmosomal junctions.
BACKGROUND
Many 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 tight and adherens junctions, the only alterations observed were in desmosomal proteins in nasal polyp epithelium compared with normal controls. Specifically, expression of desmosomal proteins DSG2 and DSG3 were significantly decreased in polyps versus controls (0.53 pixel/microm2 versus 1.09 pixel/microm2 [p = 0.009], and 0.29 pixel/microm2 versus 1.11 pixel/microm2 [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 DSG2 by immunofluorescence and Western blotting. Treatment with IFN-gamma resulted in increased expression of DSG2 and evidence of protein cleavage by Western blot. IL-13 exposure resulted in down-regulation of DSG2 expression and evidence of protein cleavage.


CONCLUSIONS
These results indicate that nasal polyps express decreased levels of DSG2 and DSG3 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 DSG2, 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.
Zuckerman
Jodi D
JD
Department of Otolaryngology-Head and Neck Surgery, Emory University School of Medicine, Atlanta, Georgia, USA.
Lee
Winston Y
WY
DelGaudio
John M
JM
Moore
Charles E
CE
Nava
Porfirio
P
Nusrat
Asma
A
Parkos
Charles A
CA
D000328:Adult; D000368:Aged; D015153:Blotting, Western; D051301:Desmoglein 2 / Q000032:analysis; D051184:Desmoglein 3 / Q000032:analysis; D003896:Desmosomes / Q000502:physiology*; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis; D018793:Interleukin-13 / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009298:Nasal Polyps / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D051301:Desmoglein 2; D051184:Desmoglein 3; D018793:Interleukin-13; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma