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Updated: Oct 17, 2025

Nasal Potential Difference to Quantify Trans-epithelial Ion Transport in Mice
Published on: July 4, 2018
Trimellitic anhydride facilitates transepithelial permeability disrupting tight junctions in sinonasal epithelial
Kazuhiro Ogi1, Sha Liu2, Mahnaz Ramezanpour2
1Department of Surgery-Otolaryngology, Head and Neck Surgery, University of Adelaide, Adelaide, South Australia, Australia; Basil Hetzel Institute for Translational Health Research, Central Adelaide Local Health Network, The Queen Elizabeth Hospital, Woodville South, South Australia, Australia; Division of Otorhinolaryngology-Head and Neck Surgery, Department of Sensory and Locomotor Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.
Abstract:
Trimellitic anhydride (TMA) is a chemical agent classified as a low molecular weight (LMW) agent causing occupational rhinitis (OR) or asthma. Although TMA is recognized as a respiratory sensitizer, the direct and non-immunologic effects of TMA remain unclear. Air- liquid interface (ALI) cultured human nasal epithelial cells (HNECs) derived from control subjects were treated with TMA, followed by measurement of the transepithelial electrical resistance (TEER), paracellular permeability of fluorescein isothiocyanate (FITC)-dextran and immunofluorescence of tight junction proteins claudin-1 and zonula occludens-1 (ZO-1). The cytotoxicity of TMA was evaluated by lactate dehydrogenase (LDH) assay. TMA at concentrations of 2 and 4 mg/mL significantly reduced the TEER within 10 min (p = 0.0177 on 2 mg/mL; p < 0.0001 on 4 mg/mL). The paracellular permeability of FITC-dextran was significantly increased upon challenge with 4 mg/mL TMA for 3 h (p = 0.0088) and 6 h (p = 0.0004). TMA treatment induced a reduction in the fluorescence intensity of claudin-1 and ZO-1 in a dose-dependent manner. LDH assay revealed 4 mg/mL TMA induced cytotoxicity only after 6 h incubation, while 1 or 2 mg/mL TMA caused no cytotoxicity. Our results suggest that TMA has a potential to penetrate the epithelial barrier by disrupting claudin-1 and ZO-1, indicating an important role for sensitization and OR development.
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