EXPRESSION OF RANTES BY HUMAN BRONCHIAL EPITHELIAL-CELLS IN-VITRO ANDIN-VIVO AND THE EFFECT OF CORTICOSTEROIDS

Recent studies have demonstrated that RANTES, a member of the CC chemo kine family affecting monocytes, T cells, basophils, and eosinophils, is expressed by several cell types. To investigate whether human bronc hial epithelial cells can also express this chemokine, we investigated human bronchial epithelial cells for their ability to synthesize RANT ES, both in vitro and in vivo. Additionally, we investigated the effec t of treatment for 4 mo with inhaled corticosteroids on the expression of RANTES in these cells in vivo. Human bronchial epithelial cells cu ltured from surgical tissue expressed the mRNA for RANTES and synthesi zed RANTES, as demonstrated by polymerase chain reaction and immunocyt ochemical staining and enzyme-linked immunosorbent assay, respectively . Incubation of the cultures with 50 ng/ml of tumor necrosis factor-al pha (TNF-alpha) significantly increased the release of RANTES into cul ture medium after 18 to 48 h of incubation, an effect that was abolish ed by treatment of the cultures with anti-TNF-alpha antibody. RANTES w as also expressed in the bronchial epithelium in vivo, as indicated by positive immunocytochemical staining of bronchial biopsy tissues obta ined from mild asthmatic patients before and after treatment with 500 mu g of inhaled beclomethasone dipropionate (BDP) twice daily or match ed placebo for 4 mo. Quantitation, by color image analysis, of the per centage of epithelium staining for RANTES showed that treatment with B DP decreased the expression of RANTES in the bronchial epithelium from 17.12% to 4.22% (P < 0.05). The numbers of EG2-staining cells in the epithelium were also reduced, from 790.1/mm(2) to 203.3/mm(2) (geometr ic mean; P < 0.01), after BDP treatment. These results suggest that hu man bronchial epithelial cells are capable of synthesizing RANTES and may therefore play an important role in the development of inflammatio n in allergic airways disease. Furthermore, corticosteroids may preven t airway inflammation by downregulating the expression of proinflammat ory cytokines in the bronchial epithelium.