Glucocorticoid-mediated repression of intercellular adhesion molecule-1 expression in human monocytic and bronchial epithelial cell lines.
Increased expression of the intercellular adhesion molecule-1 (ICAM-1) on cells present in the airways has been suggested to play a role in the pathogenesis of asthma by enhancing airway inflammation. We used the monocytic U937 cell line, both undifferentiated and differentiated to a macrophage-like phenotype, and the bronchial epithelial cell line NCI-H292 as cellular model systems for human monocytes/macrophages and bronchial epithelial cells, respectively, and studied the effects of 12-O-tetradecanoyl phorbol-13-acetate (TPA) and dexamethasone on ICAM-1 expression. Both cell lines expressed the ICAM-1 protein constitutively. In addition, TPA- or 1,25-dihydroxyvitamin D3-mediated differentiation of the U937 cell line into a macrophage-like phenotype was associated with increased expression of ICAM-1. In both cell lines, two ICAM-1 mRNA transcripts were found, and expression was stimulated to a similar degree within 1 to 2 h after addition of TPA. In both cell lines, the anti-inflammatory corticosteroid dexamethasone repressed both constitutive and TPA-stimulated ICAM-1 expression, within 3 h of its addition. In the presence of cycloheximide, a marked superinduction of ICAM-1 was observed, while the repressive effect of dexamethasone remained, supporting the hypothesis that dexamethasone acts directly at the transcriptional level.
van de Stolpe
A
A
Hubrecht Laboratory, Netherlands Institute for Developmental Biology, Utrecht.
Caldenhoven
E
E
Raaijmakers
J A
JA
van der Saag
P T
PT
Koenderman
L
L
D000911:Antibodies, Monoclonal; D001980:Bronchi / Q000166:cytology / Q000502:physiology*; D002117:Calcitriol / Q000494:pharmacology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology*; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects / Q000502:physiology; D005434:Flow Cytometry; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D007700:Kinetics; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; D003907:Dexamethasone; D002117:Calcitriol; D013755:Tetradecanoylphorbol Acetate