We conclude that expression of aminopeptidase N and dipeptidyl peptidase IV is restricted to specific sites within the human bronchus. Furthermore, in the bronchial epithelium of allergic asthmatics an increased number of aminopeptidase N-expressing dendritic cells and eosinophils can be found.

M Mo od du ul la at ti io on n o of f g gl lu uc co oc co or rt ti ic co oi id d r re ec ce ep pt to or r e ex xp pr re es ss si io on n i in n h hu um ma an n b br ro on nc ch hi ia al l e ep pi it th he el li ia al l c ce el ll l l li in ne es s b by y I IL L--1 1β, , T TN NF F--α a an nd d L LP PS S nM, respectively. Using electrophoretic mobility shift assays we demonstrated the binding of nuclear translocated GR to specific sites on deoxyribonucleic acid (DNA), named glucocorticoid responsive elements (GRE).Lipopolysaccharide (LPS) and interleukin-1β (IL-1β) significantly increased the number of GR per cell (median=312% and 171% of control, respectively; p<0.05), but significantly reduced the ligand affinity of these receptors, i.e. increased the Kd (median=410% and 145% of control, respectively; p<0.05) in BEAS 2B cells.These results indicate that the bronchial epithelium may be an actual target for glucocorticoid therapy. Inflammatory mediators, such as IL-1β and LPS, modulate the number and ligand affinity of these GR. Therefore, the response of bronchial epithelium to glucocorticoid therapy may be modulated by airway diseases associated with inflammation. Eur Respir J., 1996Respir J., , 9, 2036Respir J., -2043

No abstract

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.

In this study, we investigated the expression of lipocortin I and II (annexin I and I in the human bronchial epithelium, both in vivo and in vitro. A clear expression of lipocortin I and II protein was found in the epithelium in sections of bronchial tissue. In cultured human bronchial epithelial cells we demonstrated the expression of lipocortin I and II mRNA and protein using Northern blotting, FACScan analysis and ELISA. No induction of lipocortin I or II mRNA or protein was observed after incubation with dexamethasone. Stimulation of bronchial epithelial cells with IL-1β, TNF-α or LPS for 24 h did not affect the lipocortin I or II mRNA or protein expression, although PGE2 and 6-keto-PGF1α production was significantly increased. This IL-1β- and LPS-mediated increase in eicosanoids could be reduced by dexamethasone, but was not accompanied by an increase in lipocortin I or II expression. In human bronchial epithelial cells this particular glucocorticoid action is not mediated through lipocortin I or II induction.