T. Sekiya et al., Inducible expression of a Th2-type CC chemokine thymus- and activation-regulated chemokine by human bronchial epithelial cells, J IMMUNOL, 165(4), 2000, pp. 2205-2213
CCR4 is now known to be selectively expressed in Th2 cells. Since the bronc
hial epithelium is recognized as an important source of mediators fundament
al to the manifestation of respiratory allergic inflammation, we studied th
e expression of two functional ligands for CCR4, i.e., macrophage-derived c
hemokine (MDC) and thymus- and activation-regulated chemokine (TARC), in br
onchial epithelial cells. The bronchial epithelium of asthmatics and normal
subjects expressed TARC protein, and the asthmatics showed more intense ex
pression than the normal subjects. On the other hand, MDC expression was on
ly weakly detected in the asthmatics, but the intensity was not significant
ly different from that of normal subjects. Combination of TNF-alpha and IL-
4 induced expression of TARC protein and mRNA in bronchial epithelial A549
cells, which was slightly up-regulated by IFN-gamma, The enhancement by IFN
-gamma was more pronounced in bronchial epithelial BEAS-2B cells, and a max
imum production occurred with combination of TNF-alpha, IL-4, and IFN-gamma
. On the other hand, MDC was essentially not expressed in any of the cultur
es. Furthermore, expressions of TARC protein and mRNA were almost completel
y inhibited by glucocorticoids, These results indicate that the airway epit
helium represents an important source of TARC, which potentially plays a ro
le via a paracrine mechanism in the development of allergic respiratory dis
eases. Furthermore, the beneficial effect of inhaled glucocorticoids on ast
hma may be at least in part due to their direct inhibitory effect on TARC g
eneration by the bronchial epithelium.