An Inhibitory Effect of Dexamethasone on A549 Cell Adhesion to Neutrophils: Possible Involvement of Nuclear Factor-Kappa B

In order to clarify the effects of dexamethasone on epithelial cells at the transcription factor level, protein synthesis level and functional level, we examined neutrophil adhesion to A549 cells (an immortalized human type II alveolar epithelial cell line), expression of intercellular adhesion molecule-1 (ICAM-1), and translocation of nuclear factor-kappa B (NF-κB) into nuclei. The intranuclear localization of fluorescently stained NF-κB and an adhesion assay between neutrophils and A549 cells was analyzed quantitatively using laser scanning cytometry. ICAM-1 expression on A549 cells was measured by flow cytometric analysis. Stimulation of A549 cells with tumor necrosis factor (TNF)-α caused a time- and dose-dependent increase in their adhesiveness for neutrophils. ICAM-1 expression on A549 cells after stimulation with TNF-α for 12 h was significantly up-regulated, compared with unstimulated cells (P< 0.05). Intranuclear NF-κB was induced 10 min after stimulation with TNF-α and was increased in a TNF-α-dose-dependent manner. Dexamethasone suppressed TNF-α-induced NF-κB translocation in A549 cells by approximately 60%, ICAM-1 expression on A549 cells by approximately 40%, and A549 adhesiveness for neutrophils completely. Therefore, we suggest that the inhibition of A549 adhesiveness for neutrophils by dexamethasone may be due in part to the suppression of NF-κB entry into nuclei and ICAM-1 expression in A549 cells.