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Original Articles

Effect of corticosteroids on release of RANTES and sICAM-1 from cultured human bronchial epithelial cells, induced by TNF-alpha

We have recently demonstrated that human bronchial epithelial cells can synthesise and release several inflammatory mediators, including the factor regulated on activation, normal T-cell expressed and secreted (RANTES) and soluble intercellular adhesion molecule-1 (sICAM-1), which influence the activity of eosinophils, and may, therefore play a role in the aetiology of asthma. In this study we investigated whether corticosteroids could influence the release of these proinflammatory mediators from human bronchial epithelial cells. Human bronchial epithelial cells were cultured to confluence as explant cultures, and incubated in the presence of 50 ng x mL(-1) tumour necrosis factor-alpha (TNF-alpha) +/- 0-10(-4) M of either fluticasone propionate (FP), beclomethasone dipropionate (BDP), or hydrocortisone (HC) for 24 h. The culture medium was collected and analyzed for RANTES and sICAM-1, by enzyme-linked immunosorbent assay (ELISA), and the cells were analysed for total protein. The TNF-alpha significantly increased the release both of RANTES and sICAM-1 (63.0 fg RANTES x microg(-1) protein; p<0.05; 8.8 pg sICAM-1 x microg(-1) protein; p<0.02), when compared with untreated cells (10.3 fg RANTES x microg(-1) protein; 2.6 pg sICAM-1 x microg(-1) cellular protein). The TNF-alpha-induced release both of RANTES and sICAM-1 occurred in a time-dependent manner, and was maximal by 24 h incubation. FP 10(-6)-10(-4) M significantly attenuated the TNF-alpha-induced release both of RANTES and sICAM-1. In contrast, 10(-4) M BDP or HC significantly attenuated the release of only sICAM-1. These results suggest that corticosteroids may prevent airway inflammation by downregulating the synthesis and/or release of proinflammatory mediators from bronchial epithelial cells. Furthermore, fluticasone propionate may be more efficacious than beclomethasone dipropionate or hydrocortisone in this respect.

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