Abstract
Background: Dermatophagoides pteronyssinus 1/2 (Der p 1/Der p 2) are regarded as important allergens of house dust mite (HDM). However, the effect of both products on the epithelial barrier and immune response of patients with and without HDM allergic rhinitis (AR) remains unclear.Methods: Air–liquid interface (ALI) cultured human nasal epithelial cells (HNECs) derived from control subjects (non-AR) (n = 9) and HDM-AR patients (n = 9) were treated with Der P 1 and Der P 2, followed by testing the transepithelial electrical resistance (TEER), paracellular permeability of fluorescein isothiocyanate (FITC)-dextrans and immunofluorescence of claudin-1 and ZO-1. Interleukin-6 (IL-6) production was evaluated by ELISA.Results: Der p 1 reduced TEER significantly in a transient and dose-dependent manner in HNEC-ALI cultures from HDM-AR and non-AR patients, whilst the paracellular permeability was not affected. TEER was significantly reduced by Der p 1 at the 10-min time point in HDM-AR patients compared to non-AR patients (p = 0.0259). Compared to no-treatment control, in HNECs derived from HDM-AR patients, Der p 1 significantly cleaved claudin-1 after 30 min exposure (72.7 ± 9.5 % in non-AR group, 39.9 ± 7.1 % in HDM-AR group, p = 0.0286) and induced IL-6 secretion (p = 0.0271).Conclusions: Our results suggest that patients with HDM-AR are more sensitive to Der p 1 than non-AR patients with increased effects of Der p1 on the mucosal barrier and induction of inflammation, indicating an important role for Der p1 in sensitization and HDM-AR development.
Highlights
Allergic rhinitis (AR) is a common disorder involving immunoglobulin E (IgE)-mediated type I allergic inflammation of the nasal mucosa following allergen exposure [1]
In HNECALI cultures derived from both house dust mites (HDM)-AR and non-AR patients, Der p 1 affected Transepithelial Electrical Resistance (TEER) in a transient, dose- and time-dependent manner with a significant reduction in TEER in Der p 1 challenged cells compared to control at the 30-min (p = 0.0021 for 2 mM and p < 0.0001 for 4 mM in non-AR group; p = 0.0085 for 2mM and p < 0.0001 for 4mM in HDM-allergic rhinitis (HDM-AR) group) and 1-h time point (p = 0.0031 for 4mM in non-AR group; p = 0.0030 for 4mM in HDM-AR group) (Figures 1A,B)
A significant reduction in TEER was observed in human nasal epithelial cell (HNEC)-air-liquid interface (ALI) cultures treated with 4 mM Der p 1 at the 10-min time point in cells derived from HDMAR patients (p = 0.0321) but not in cells derived from non-AR patients (p = 0.1136)
Summary
Allergic rhinitis (AR) is a common disorder involving immunoglobulin E (IgE)-mediated type I allergic inflammation of the nasal mucosa following allergen exposure [1]. The most common environmental factors leading to the development of AR are allergens, and house dust mites (HDM) are the most common aeroallergens worldwide in perennial AR and allergic asthma [3]. Der p 1 is a 25kDa protein and has enzymatic activity as a cysteine protease. It is classified as a digestive tract enzyme as Der p 1 is found mainly in the excrement of mites. Der p 2 is a 14-kDa protein, mainly found in the body of mites rather than excrement. Dermatophagoides pteronyssinus 1/2 (Der p 1/Der p 2) are regarded as important allergens of house dust mite (HDM). The effect of both products on the epithelial barrier and immune response of patients with and without HDM allergic rhinitis (AR) remains unclear
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