Jh. Wang et al., EXPRESSION OF RANTES BY HUMAN BRONCHIAL EPITHELIAL-CELLS IN-VITRO ANDIN-VIVO AND THE EFFECT OF CORTICOSTEROIDS, American journal of respiratory cell and molecular biology, 14(1), 1996, pp. 27-35
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.