Jh. Wang et al., EFFECT OF CORTICOSTEROIDS ON RELEASE OF RANTES AND SICAM-1 FROM CULTURED HUMAN BRONCHIAL EPITHELIAL-CELLS, INDUCED BY TNF-ALPHA, The European respiratory journal, 10(4), 1997, pp. 834-840
We have recently demonstrated that human bronchial epithetial cells ca
n 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), whi
ch influence the activity of eosinophils, and may, therefore play a ro
le in the aetiology of asthma. In this study we investigated whether c
orticosteroids could influence the release of these proinflammatory me
diators from human bronchial epithelial cells. Human bronchial epithel
ial cells were cultured to confluence as explant cultures, and incubat
ed in the presence of 50 ng.mL(-1) tumour necrosis factor-alpha (TNF-a
lpha +/-0-10(-4) M of either fluticasone propionate (FP), beclomethaso
ne dipropionate (BDP), or hydrocortisone (HC) for 24 h. The culture me
dium was collected and analyzed for RANTES and sICAM-1, by enzyme-link
ed immunosorbent assay (ELISA), and the cells were analysed for total
protein. The ThF-alpha significantly increased the release both of RAN
TES and sICAM-1 (63.0 fg RANTES mu g(-1) protein; p<0.05; 8.8 pg sICAM
-1.mu g(-1) protein; p<0.02), when compared with untreated cells (10.3
fg RANTES.mu g(-1) protein; 2.6 pg sICAM-1.mu g(-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 cor
ticosteroids may prevent airway inflammation by downregulating the syn
thesis and/or release of proinflammatory mediators from bronchial epit
helial cells. Furthermore, fluticasone propionate may be more efficaci
ous than beclomethasone dipropionate or hydrocortisone in this respect
.