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.
ABSTRACT
BACKGROUND: Angiopoietin (Ang)-1 and -2 are involved in the pathogenesis of asthma and have been identified as markers of asthma severity. OBJECTIVE: To determine the relation between circulating angiopoietins and clinical variables of patients with asthma. METHODS: Fifty patients with bronchial asthma and 25 healthy controls were enrolled. Ang1 and Ang2 plasma levels were analyzed in patients with stable and exacerbated asthma. RESULTS: Plasma Ang1 levels were 28.4 ± 4.01 pg/mg in patients with bronchial asthma and 21.2 ± 5.21 pg/mg in healthy controls. Plasma Ang2 levels were 23.96 ± 1.38 pg/mg in patients with bronchial asthma compared with 36.8 ± 4.46 pg/mg in healthy controls (P = .010). The ratio of Ang2 to Ang1 was lower in patients with asthma than in control subjects. Plasma Ang1 concentrations were correlated with the ratio of forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC), and plasma Ang2 levels were correlated with FEV1 percentage of predicted, FEV1/FVC, and total immunoglobulin E values. The ratio of Ang2 to Ang1 was correlated with FEV1 percentage of predicted and FEV1/FVC. Although plasma Ang1 levels tended to be lower in the exacerbated state than in the stable state in patients with asthma, Ang2 levels were higher in the exacerbated state than in the stable state in patients with asthma (P = .001). Plasma Ang2 levels were correlated with initial eosinophil proportions and initial neutrophil proportions. Plasma Ang2 levels and the ratio of Ang2 to Ang1 were correlated with blood eosinophil proportions in the exacerbated state. CONCLUSION: These results indicate that circulating angiopoietins could be a useful marker of asthma exacerbation.
