Epithelial tight junction alterations in nasal polyposis.

OBJECTIVE

To explore alterations in expression of tight junction proteins (TJPs) in nasal polyposis and in respiratory epithelium under inflammatory conditions. Our hypothesis is that exposure of nasal and respiratory epithelium to inflammatory cytokines results in the altered expression of specific TJPs.

METHODS

Human sinonasal mucosa (3 nasal polyp specimens and 3 nonpolypoid controls) were stained with immunofluorescent markers specific for TJPs claudin-1 and occludin and examined with confocal scanning laser microscopy. A complementary in vitro experiment involving exposure of cultured human bronchial epithelium to interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α) was also performed. Alterations in claudin-1 and occludin were localized by immunofluorescence labeling and confocal microscopy and quantified by western blotting.

RESULTS

Nasal polyp epithelium from human tissue specimens had reduced claudin-1 expression along the basal aspect of the mucosal layer, whereas occludin expression was reduced in the apical and basal epithelial zones. In vitro experiments demonstrated stable or increased TJP expression after 24 hours of cytokine exposure (43% increase for claudin-1, 9% increase for occludin). However, a reduction in TJP expression was observed after 72 hours of cytokine exposure (18% reduction for claudin-1, and 43% reduction for occludin).

CONCLUSION

Nasal polyposis is associated with epithelial TJP alterations. Further, the expression of TJPs in a model of inflamed respiratory mucosa is reduced in a similar fashion. Research on the histopathology of other epithelial inflammatory disorders suggests TJP alterations contribute to a self-perpetuating inflammatory state. Findings of this preliminary study support a similar process in nasal polyposis.