Inducible expression of a Th2-type CC chemokine thymus- and activation-regulated chemokine by human bronchial epithelial cells

Citation
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
Citations number
37
Categorie Soggetti
Immunology
Journal title
JOURNAL OF IMMUNOLOGY
ISSN journal
00221767 → ACNP
Volume
165
Issue
4
Year of publication
2000
Pages
2205 - 2213
Database
ISI
SICI code
0022-1767(20000815)165:4<2205:IEOATC>2.0.ZU;2-7
Abstract
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.