Unknown

Dataset Information

0

Claudin-18 deficiency is associated with airway epithelial barrier dysfunction and asthma.


ABSTRACT: BACKGROUND:Epithelial barrier dysfunction and increased permeability may contribute to antigen sensitization and disease progression in asthma. Claudin-18.1 is the only known lung-specific tight junction protein, but its contribution to airway barrier function or asthma is unclear. OBJECTIVES:We sought to test the hypotheses that claudin-18 is a determinant of airway epithelial barrier function that is downregulated by IL-13 and that claudin-18 deficiency results in increased aeroantigen sensitization and airway hyperresponsiveness. METHODS:Claudin-18.1 mRNA levels were measured in airway epithelial brushings from healthy controls and patients with asthma. In patients with asthma, claudin-18 levels were compared with a three-gene-mean marker of TH2 inflammation. Airway epithelial permeability changes due to claudin-18 deficiency were measured in 16HBE cells and claudin-18 null mice. The effect of IL-13 on claudin expression was determined in primary human airway epithelial cells and in mice. Airway hyperresponsiveness and serum IgE levels were compared in claudin-18 null and wild-type mice following aspergillus sensitization. RESULTS:Epithelial brushings from patients with asthma (n = 67) had significantly lower claudin-18 mRNA levels than did those from healthy controls (n = 42). Claudin-18 levels were lowest among TH2-high patients with asthma. Loss of claudin-18 was sufficient to impair epithelial barrier function in 16HBE cells and in mouse airways. IL-13 decreased claudin-18 expression in primary human cells and in mice. Claudin-18 null mice had significantly higher serum IgE levels and increased airway responsiveness following intranasal aspergillus sensitization. CONCLUSIONS:These data support the hypothesis that claudin-18 is an essential contributor to the airway epithelial barrier to aeroantigens. Furthermore, TH2 inflammation suppresses claudin-18 expression, potentially promoting sensitization and airway hyperresponsiveness.

SUBMITTER: Sweerus K 

PROVIDER: S-EPMC5073041 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

altmetric image

Publications

Claudin-18 deficiency is associated with airway epithelial barrier dysfunction and asthma.

Sweerus Kelly K   Lachowicz-Scroggins Marrah M   Gordon Erin E   LaFemina Michael M   Huang Xiaozhu X   Parikh Mihir M   Kanegai Cindy C   Fahy John V JV   Frank James A JA  

The Journal of allergy and clinical immunology 20160420 1


<h4>Background</h4>Epithelial barrier dysfunction and increased permeability may contribute to antigen sensitization and disease progression in asthma. Claudin-18.1 is the only known lung-specific tight junction protein, but its contribution to airway barrier function or asthma is unclear.<h4>Objectives</h4>We sought to test the hypotheses that claudin-18 is a determinant of airway epithelial barrier function that is downregulated by IL-13 and that claudin-18 deficiency results in increased aero  ...[more]

Similar Datasets

| S-EPMC10160377 | biostudies-literature
| S-EPMC5962552 | biostudies-literature
| S-EPMC5723110 | biostudies-literature
2018-06-30 | GSE106233 | GEO
| S-EPMC7518063 | biostudies-literature
| S-EPMC7893966 | biostudies-literature
| S-EPMC10754389 | biostudies-literature
| S-EPMC8000923 | biostudies-literature
| S-EPMC9990325 | biostudies-literature
| S-EPMC8920196 | biostudies-literature