Glucocorticoid receptor expression in human bronchial epithelial cells: effects of smoking and COPD.
Previously, we found that inflammatory mediators modulated the number and binding affinity of glucocorticoid receptors (GR) in human bronchial epithelial cell lines. In this study we investigated whether smoking and chronic obstructive pulmonary disease (COPD), both characterized by airway inflammation with increased levels of inflammatory mediators, affect GR characteristics in cultured human bronchial epithelial cells (HBEC). A statistically significant difference was found between the dissociation constant (Kd) values in HBEC from smoking (Kd = 0.98+/-0.08 nM; n = 6) and nonsmoking controls (Kd = 0.76+/-0.10 nM, P = 0.03; n = 5), but no significant difference was found between the mean number of binding sites. Our results are the first indication that cultured HBEC from smokers possess GR with a lower binding affinity. This may result from the inflammation found in the airways from smokers. Furthermore, these results provide further evidence that the bronchial epithelium may be an actual target for inhaled glucocorticoid therapy.
Verheggen
M M
MM
Department of Immunology, Erasmus University and University Hospital Rotterdam-Dijkzigt, Rotterdam, The Netherlands.
Adriaansen-Soeting
P W
PW
Berrevoets
C A
CA
van Hal
P T
PT
Brinkmann
A O
AO
Hoogsteden
H C
HC
Versnel
M A
MA
D000368:Aged; D001665:Binding Sites; D001980:Bronchi / Q000737:chemistry*; D002460:Cell Line; D003907:Dexamethasone / Q000378:metabolism; D004847:Epithelial Cells / Q000737:chemistry; D006801:Humans; D008173:Lung Diseases, Obstructive / Q000378:metabolism*; D008875:Middle Aged; D011965:Receptors, Glucocorticoid / Q000032:analysis*; D012907:Smoking / Q000378:metabolism*
D011965:Receptors, Glucocorticoid; D003907:Dexamethasone