Altered sinonasal epithelial ion transport in patients with chronic rhinosinusitis

Chronic rhinosinusitis (CRS) is considered a common chronic disorder. The pathophysiologic mechanisms are still not entirely known and may be linked to altered ion transport by the nasal epithelium. Purpose of this study was to evaluate whether the epithelial ion transport is affected in cultured human nasal epithelial primary cells (hNEpC) of patients with CRS. Further we determined the epithelial expression of pro-inflammatory cytokines.

hNEpC were freshly isolated from the paranasal sinuses of consenting patients undergoing FESS. Tissue of the lower turbinate was obtained from healthy controls. HNEpC were cultured under air-liquid-interface conditions and the transepithelial short-circuit current (Isc) was measured in the absence and presence of pre-treatment with IL-13 using a Cl^– gradient. Transcript levels of ion channels were determined using real-time PCR.

Ussing chamber studies demonstrated a significantly reduced basal Isc in hNEpC cell monolayers of patients with CRS compared to healthy controls.

The amiloride-sensitive Isc and the UTP-induced responses were substantially lower in CRS. On mRNA level, transcript levels of β- and γ-ENaC as well as P₂Y₂, were significantly reduced. In contrast to functional evidence, mRNA levels of TMEM16A were significantly increased. The cytokine analysis showed a significant increase in mRNA levels of IFN-γ and IL-13 in CRS cultures, whereas IL-1β was diminished compared to CTL.

We observed a complex dysregulation of ion transport dominated by reduced basal Isc and Ca⁺-activated Cl^– secretion across cultured nasal epithelial cells of patients with CRS. Our data suggest that TMEM16A-mediated Cl^– secretion might be implicated in the pathogenesis of CRS.

Publication History

Publication Date:
18 April 2018 (online)