1. Histamine and T helper cytokine driven epithelial barrier dysfunction in allergic rhinitis
- Author
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Laura Van Gerven, Ulrike Raap, Guy E. Boeckxstaens, Brecht Steelant, Peter Hellings, Matthias Van Woensel, Cezmi A. Akdis, Paulina Wawrzyniak, Inge Kortekaas Krohn, Ricard Farré, Jan Ceuppens, Sven Seys, Louis Boon, Karel Talavera, Dominique Bullens, Dermatology, Ear, Nose and Throat, University of Zurich, and Hellings, Peter W
- Subjects
0301 basic medicine ,Male ,tight junctions ,Allergy ,PROTEIN EXPRESSION ,medicine.medical_treatment ,CHRONIC RHINOSINUSITIS ,UP-REGULATION ,Allergic rhinitis ,idiopathic rhinitis ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,10183 Swiss Institute of Allergy and Asthma Research ,Immunologie ,Immunology and Allergy ,Fluorescein isothiocyanate ,Mice, Inbred BALB C ,Tight junction ,INFLAMMATORY CELLS ,TNF-ALPHA ,CROHNS-DISEASE ,Cytokine ,Paracellular transport ,2723 Immunology and Allergy ,Cytokines ,CAPSAICIN TREATMENT ,Female ,Life Sciences & Biomedicine ,Histamine ,medicine.drug ,Allergie et immunopathologie ,Immunology ,610 Medicine & health ,TIGHT JUNCTION BARRIER ,primary nasal epithelial cells ,Cell Line ,03 medical and health sciences ,Immune system ,Th2 Cells ,Downregulation and upregulation ,medicine ,Animals ,Humans ,T(H)2 cells ,2403 Immunology ,Science & Technology ,allergic rhinitis ,business.industry ,NECROSIS-FACTOR-ALPHA ,Th1 Cells ,T 2 cells ,Azelastine ,Rhinitis, Allergic ,histamine ,Nasal Mucosa ,030104 developmental biology ,030228 respiratory system ,chemistry ,TH2 cells ,business - Abstract
Background: Allergic rhinitis (AR) is characterized by mucosal inflammation, driven by activated immune cells. Mast cells and TH2 cells might decrease epithelial barrier integrity in AR, maintaining a leaky epithelial barrier. Objective: We sought to investigate the role of histamine and TH2 cells in driving epithelial barrier dysfunction in AR. Methods: Air-liquid interface cultures of primary nasal epithelial cells were used to measure transepithelial electrical resistance, paracellular flux of fluorescein isothiocyanate-dextran 4 kDa, and mRNA expression of tight junctions. Nasal secretions were collected from healthy control subjects, AR patients, and idiopathic rhinitis patients and were tested in vitro. In addition, the effect of activated TH1 and TH2 cells, mast cells, and neurons was tested in vitro. The effect of IL-4, IL-13, IFN-γ and TNF-α on mucosal permeability was tested in vivo. Results: Histamine as well as nasal secretions of AR but not idiopathic rhinitis patients rapidly decreased epithelial barrier integrity in vitro. Pretreatment with histamine receptor-1 antagonist, azelastine prevented the early effect of nasal secretions of AR patients on epithelial integrity. Supernatant of activated TH1 and TH2 cells impaired epithelial integrity, while treatment with anti-TNF-α or anti-IL-4Rα monoclonal antibodies restored the TH1- and TH2-induced epithelial barrier dysfunction, respectively. IL-4, IFN-γ and TNF-α enhanced mucosal permeability in mice. Antagonizing IL-4 prevented mucosal barrier disruption and tight junction downregulation in a mouse model of house dust mite allergic airway inflammation. Conclusions: Our data indicate a key role for allergic inflammatory mediators in modulating nasal epithelial barrier integrity in the pathophysiology in AR., SCOPUS: ar.j, info:eu-repo/semantics/published
- Published
- 2018