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 t he 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 an d 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 constituti vely. In addition, TPA- or 1,25-dihydroxyvitamin D3-mediated different iation of the U937 cell line into a macrophage-like phenotype was asso ciated with increased expression of ICAM-1. In both cell lines, two IC AM-1 mRNA transcripts were found, and expression was stimulated to a s imilar degree within 1 to 2 h after addition of TPA. In both cell line s, the anti-inflammatory corticosteroid dexamethasone repressed both c onstitutive and TPA-stimulated ICAM-1 expression, within 3 h of its ad dition. In the presence of cycloheximide, a marked superinduction of I CAM-1 was observed, while the repressive effect of dexamethasone remai ned, supporting the hypothesis that dexamethasone acts directly at the transcriptional level.