EXPRESSION OF RANTES IN HUMAN AIRWAY EPITHELIAL-CELLS - EFFECT OF CORTICOSTEROIDS AND INTERLEUKIN-4, INTERLEUKIN-10 AND INTERLEUKIN-13

RANTES is a C-C chemokine with strong chemoattractant and activating p roperties for eosinophils, basophils and T lymphocytes. We investigate d the expression of RANTES in human airway epithelial cells and its mo dulation. Epithelial cells obtained from tracheas of donor lungs were stimulated with interleukin-1 beta (IL-1 beta), tumour necrosis factor -alpha (TNF-alpha), interferon-gamma (IFN-gamma) or with a mixture of the three cytokines ('cytomix'). Levels of mRNA and protein were assay ed by Northern blot and radioimmunoassay, respectively. Each individua l cytokine produced a small increase in RANTES protein: IL-1 beta 24 /- 1 pM, TNF-alpha 13 +/- 7 pM and IFN-gamma, 29 +/- 7 pM, but cytomix increased protein to 236 +/- 22 pM (P < 0.002) and mRNA expression by >20-fold (P < 0.002). Both RANTES protein and mRNA expression were in hibited by dexamethasone (10(-6) M) (38 +/- 5%, P < 0.05 and 55 +/- 8% , P < 0.007, respectively), and by IL-4 (42 +/- 7%, P < 0.03 and 19 +/ - 1%, not significant, respectively). No inhibitory effect was observe d with IL-10 or IL-13. We also demonstrated in vivo expression of RANT ES protein by epithelial cells in human airways using immunohistochemi stry. Our data show that human airway epithelial cells can be stimulat ed to express and release RANTES, an effect that is inhibited by corti costeroids and IL-4, but not by IL-10 and IL-13.