Corticosteroids and montelukast: effects on airway epithelial and human umbilical vein endothelial cells.
Our primary objective was to investigate the possible contribution of controller medications to asthmatic airway remodeling, by (1) comparing the apoptotic and necrotic effects of several corticosteroids and montelukast on cultured airway human bronchial surface epithelial (16HBE) and submucosal (Calu3) cells; (2) measuring epithelial shedding potential and desmosome length in response to a cytokine challenge, with or without co-administered corticosteroids; and (3) studying corticosteroids and montelukast effects on inter-cellular adhesion molecule (ICAM) expression in both 16HBE and human umbilical vein endothelial cells (HUVEC). For this purpose, apoptosis, necrosis, and ICAM expression were quantified by flow cytometry, with 16HBE cells sensitive to both the apoptotic and necrotic effects of dexamethasone and montelukast; Calu3 cells sensitive only to budesonide. Transmission electron microscopy revealed decreased desmosome length in the presence of cytokines (TNF-alpha and INF-gamma), with corticosteroids counteracting this reduction. Dexamethasone, beclomethasone, and montelukast decreased versus increased ICAM-1 expression in airway epithelial cells and HUVEC, respectively. For conclusions, bronchial surface epithelial and submucosal cells exhibit a different sensitivity profile toward dexamethasone, budesonide, and montelukast, with corticosteroids preventing cytokineinduced desmosomal damage in 16HBE cells. The studied drugs led to increased ICAM-1 expression in endothelium, potentially facilitating inflammatory cell migration into lung tissue.
Andersson
K
K
Department of Medical Cell Biology, University of Uppsala, Box 571, 75123, Uppsala, Sweden.
Shebani
E B
EB
Makeeva
N
N
Roomans
G M
GM
Servetnyk
Z
Z
D000085:Acetates / Q000494:pharmacology* / Q000627:therapeutic use; D000305:Adrenal Cortex Hormones / Q000494:pharmacology* / Q000627:therapeutic use; D018927:Anti-Asthmatic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001249:Asthma / Q000188:drug therapy / Q000473:pathology*; D002460:Cell Line; D003521:Cyclopropanes; D016207:Cytokines / Q000494:pharmacology; D003896:Desmosomes / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D020024:Leukotriene Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D009336:Necrosis; D011804:Quinolines / Q000494:pharmacology* / Q000627:therapeutic use; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000473:pathology; D013440:Sulfides; D014471:Umbilical Veins / Q000187:drug effects / Q000473:pathology
D000085:Acetates; D000305:Adrenal Cortex Hormones; D018927:Anti-Asthmatic Agents; D003521:Cyclopropanes; D016207:Cytokines; D020024:Leukotriene Antagonists; D011804:Quinolines; D013440:Sulfides; D018799:Intercellular Adhesion Molecule-1; C093875:montelukast