Differentiation of human bronchial epithelial cells: role of hydrocortisone in development of ion transport pathways involved in mucociliary clearance.
Glucocorticoids strongly influence the mucosal-defense functions performed by the bronchial epithelium, and inhaled corticosteroids are critical in the treatment of patients with inflammatory airway diseases such as asthma, chronic obstructive pulmonary disease, and cystic fibrosis. A common pathology associated with these diseases is reduced mucociliary clearance, a defense mechanism involving the coordinated transport of salt, water, and mucus by the bronchial epithelium, ultimately leading to retention of pathogens and particles in the airways and to further disease progression. In the present study we investigated the role of hydrocortisone (HC) in differentiation and development of the ion transport phenotype of normal human bronchial epithelial cells under air-liquid interface conditions. Normal human bronchial epithelial cells differentiated in the absence of HC (HC0) showed significantly less benzamil-sensitive short-circuit current than controls, as well as a reduced response after stimulation with the selective β2-adrenergic receptor agonist salbutamol. Apical membrane localization of epithelial Na(+) channel α-subunits was similarly reduced in HC0 cells compared with controls, supporting a role of HC in the trafficking and density of Na(+) channels in the plasma membrane. Additionally, glucocorticoid exposure during differentiation regulated the transcription of cystic fibrosis transmembrane conductance regulator and β2-adrenergic receptor mRNAs and appeared to be necessary for the expression of cystic fibrosis transmembrane conductance regulator-dependent anion secretion in response to β2-agonists. HC had no significant effect on surface cell differentiation but did modulate the expression of mucin mRNAs. These findings indicate that glucocorticoids support mucosal defense by regulating critical transport pathways essential for effective mucociliary clearance.
Department of Integrative Biology and Physiology, University of Minnesota, Minneapolis, Minnesota;
Nathan A
NA
Zaidman
Department of Integrative Biology and Physiology, University of Minnesota, Minneapolis, Minnesota; Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota; and.
Angela
A
Panoskaltsis-Mortari
Department of Integrative Biology and Physiology, University of Minnesota, Minneapolis, Minnesota; Department of Animal Science, University of Minnesota, Minneapolis, Minnesota ograd001@umn.edu.
Scott M
SM
O'Grady
D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D003550:Cystic Fibrosis / Q000378:metabolism / Q000503:physiopathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D053503:Epithelial Sodium Channels / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D017136:Ion Transport / Q000187:drug effects / Q000502:physiology*; D009077:Mucins / Q000378:metabolism; D009079:Mucociliary Clearance / Q000187:drug effects / Q000502:physiology*; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D012964:Sodium / Q000378:metabolism
D053503:Epithelial Sodium Channels; D009077:Mucins; D018343:Receptors, Adrenergic, beta-2; C013407:benzamil; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D000584:Amiloride; D012964:Sodium; D006854:Hydrocortisone
cystic fibrosis transmembrane conductance regulator; epithelial ion transport; epithelial sodium channel; salbutamol; β2-adrenergic receptors