Alteration in Claudin-4 Contributes to Airway Inflammation and Responsiveness in Asthma
10.4168/aair.2018.10.1.25
- Author:
Pureun Haneul LEE
1
;
Byeong Gon KIM
;
Sun Hye LEE
;
June Hyuck LEE
;
Sung Woo PARK
;
Do Jin KIM
;
Choon Sik PARK
;
George D LEIKAUF
;
An Soo JANG
Author Information
1. Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea. jas877@schmc.ac.kr
- Publication Type:Original Article
- Keywords:
Asthma;
epithelial barrier;
claudin-4
- MeSH:
Animals;
Asthma;
Claudin-4;
Claudins;
Cytokines;
Eosinophils;
Epithelial Cells;
Humans;
Immunoglobulin E;
Inflammation;
Lung;
Mice;
Ovum;
Plasma;
RNA, Small Interfering;
Sodium
- From:Allergy, Asthma & Immunology Research
2018;10(1):25-33
- CountryRepublic of Korea
- Language:English
-
Abstract:
PURPOSE: Claudin-4 has been reported to function as a paracellular sodium barrier and is one of the 3 major claudins expressed in lung alveolar epithelial cells. However, the possible role of claudin-4 in bronchial asthma has not yet been fully studied. In this study, we aimed to elucidate the role of claudin-4 in the pathogenesis of bronchial asthma. METHODS: We determined claudin-4 levels in blood from asthmatic patients. Moreover, using mice sensitized and challenged with OVA, as well as sensitized and challenged with saline, we investigated whether claudin-4 is involved in the pathogenesis of bronchial asthma. Der p1 induced the inflammatory cytokines in NHBE cells. RESULTS: We found that claudin-4 in blood from asthmatic patients was increased compared with that from healthy control subjects. Plasma claudin-4 levels were significantly higher in exacerbated patients than in control patients with bronchial asthma. The plasma claudin-4 level was correlated with eosinophils, total IgE, FEV1% pred, and FEV1/FVC. Moreover, lung tissues from the OVA-OVA mice showed significant increases in transcripts and proteins of claudin-4 as well as in TJ breaks and the densities of claudin-4 staining. When claudin-4 was knocked down by transfecting its siRNA, inflammatory cytokine expressions, which were induced by Der p1 treatment, were significantly increased. CONCLUSIONS: These findings thus raise the possibility that regulation of lung epithelial barrier proteins may constitute a therapeutic approach for asthma.
