BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is one of the most common chronic disorders with limited therapeutic options. However, the pathogenesis of CRSwNP remains poorly understood. OBJECTIVE: To determine the role of abnormalities in nasal epithelial ion transport in primary epithelial cultures and patients with CRSwNP. METHODS: We studied epithelial ion transport and transcript levels of the Cl(-) channels CFTR and TMEM16A in human primary nasal epithelial cultures of patients with CRSwNP and healthy controls. Further, we determined expression levels of pro-inflammatory cytokines that have been implicated in the regulation of epithelial ion channels (IL-1β, INFγ, TNFα, IL-13) and studied effects of the key Th2 signaling molecule IL-13 in CRSwNP and control nasal epithelial cultures. Finally, we measured in vivo nasal potential difference (NPD) to compare epithelial ion transport in patients with CRSwNP and controls. RESULTS: Bioelectric studies demonstrated that Ca(2+)-activated Cl(-) secretion was reduced in CRSwNP vs. control nasal epithelial cultures. Transcript levels of IL-13 and the Ca(2+)-activated Cl(-) channel TMEM16A were increased in CRSwNP cultures. Stimulation with IL-13 increased TMEM16A expression further and restored Ca(2+)-activated Cl(-) secretion in CRSwNP cultures. NPD measurements demonstrated reduced Ca(2+)-activated Cl(-) transport in CRSwNP patients vs. controls. CONCLUSION: This study demonstrates that TMEM16A-mediated Ca(2+)-activated Cl(-) secretion is reduced in primary nasal epithelial cultures and nasal epithelia of patients with CRSwNP.
- Salomon, J. J.
- Albrecht, T.
- Graeber, S. Y.
- Scheuermann, H.
- Butz, S.
- Schatterny, J.
- Mairbäurl, H.
- Baumann, I.
- Mall, M. A.
Keywords
- Ca2+-activated Cl- channel
- Chronic rhinosinusitis with nasal polyps
- Tmem16a
- epithelial Cl- transport
- nasal epithelium
