Background: Chronic rhinosinusitis (CRS) is a common chronic respiratory condition, frequently associated with asthma and affecting the majority of cystic fibrosis (CF) patients. Pseudomonas aeruginosa infections and biofilms have been implicated in recalcitrant CRS. One of the mechanisms of action for bacteria in CRS and CF is mucosal barrier disruption by secreted products that contribute to the inflammation. However, the role of biofilm and planktonic forms of P. aeruginosa in this process is not known.The aim is to determine the effect of P. aeruginosa exoproteins isolated from CF and non-CF CRS patients on the mucosal barrier. Methods: Exoproteins from 40 P. aeruginosa isolates were collected in planktonic and biofilm forms and applied to air-liquid interface (ALI) cultures of primary human nasal epithelial cells (HNECs). Mucosal barrier integrity was evaluated by transepithelial electrical resistance (TEER), passage of FITC-dextrans and immunofluorescence of tight junction proteins. Cytotoxicity assays were performed to measure cell viability, and IL-6 ELISA was carried out to evaluate pro-inflammatory effects.Results: Planktonic exoproteins from 20/40 (50%) clinical isolates had a significant detrimental effect on the barrier and significantly increased IL-6 production. Barrier disruption was characterized by a reduced TEER, increased permeability of FITCdextrans and discontinuous immunolocalization of tight junction proteins and was significantly more prevalent in isolates harvested from patients with comorbid asthma (P < .05).
Conclusion:Exoproteins from planktonic P. aeruginosa clinical isolates from asthmatic CRS patients have detrimental effects on the mucosal barrier and induce IL-6 production potentially contributing to the mucosal inflammation in CRS patients.
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.
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