Expression of RANTES in human airway epithelial cells: effect of corticosteroids and interleukin-4, -10 and -13

Abstract

RANTES is a C-C chemokine with strong chemoattractant and activating properties for eosinophils, basophils and T lymphocytes. We investigated the expression of RANTES in human airway epithelial cells and its modulation. 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 assayed by Northern blot and radioimmunoassay, respectively. Each individual 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 inhibited 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 observed with IL-10 or IL-13. We also demonstrated in vivo expression of RANTES protein by epithelial cells in human airways using immunohistochemistry. Our data show that human airway epithelial cells can be stimulated to express and release RANTES, an effect that is inhibited by corticosteroids and IL-4, but not by IL-10 and IL-13.