Glucocorticoids enhance airway epithelial barrier integrity.
Asthma is a chronic inflammatory disorder of the airways, but its pathogenesis is incompletely understood. While asthma is a complex disease caused by multiple factors, epithelial barrier damage is a cardinal feature. Glucocorticoids (GCs) are the most effective anti-inflammatory drugs in the treatment of asthma. However, the effects of GCs on the airway epithelial barrier have not been evaluated. Epithelial barrier functions were evaluated in cultured human airway epithelial cell monolayers, Calu-3 and 16HBE. Then, the cells were treated with dexamethasone (Dex), fulticasone propionate (FP), or budesonide (BD) for 5 days. Permeability measured by transepithelial electrical resistance was increased by treatment with Dex, FP, and BD in a dose-dependent manner. Permeability to fluorescein isothiocyanate-labeled dextran was markedly reduced by these treatments. Immunocytostaining revealed that Dex treatment potentiated tight junction formation in these polarized epithelial cells. Knockdown of epidermal growth factor receptor (EGFR) by small interference RNA blunted the effects of Dex on barrier integrity. Although EGFR expression was not affected by Dex treatment, EGFR phosphorylation was enhanced in Dex-treated cells. This is suggesting that EGFR are important for this phenomenon. These findings suggest that GC inhalation therapy can improve epithelial barrier integrity and might contribute to the therapeutic effects of GCs for treating asthma.
Division of Respiratory Medicine, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan.
Akiko
A
Sekiyama
Yasuhiro
Y
Gon
Masahiro
M
Terakado
Ikuko
I
Takeshita
Yutaka
Y
Kozu
Shuichiro
S
Maruoka
Ken
K
Matsumoto
Shu
S
Hashimoto
D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D019819:Budesonide / Q000494:pharmacology; D002461:Cell Line, Transformed; D003907:Dexamethasone / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D010539:Permeability / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D020545:Respiratory Mucosa / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D019819:Budesonide; D003907:Dexamethasone; C512478:EGFR protein, human; D066246:ErbB Receptors