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Histamine and T helper cytokine driven epithelial barrier dysfunction in allergic rhinitis
- Source :
- Journal of allergy and clinical immunology, 141(3), 951-963. Mosby Inc., Journal of allergy and clinical immunology, 141 (3
- Publication Year :
- 2018
-
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.<br />SCOPUS: ar.j<br />info:eu-repo/semantics/published
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 00916749
- Volume :
- 141
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Journal of allergy and clinical immunology
- Accession number :
- edsair.doi.dedup.....86ca87a500cb80607088b36e2aa86b01