Glucocorticoid receptors in alveolar macrophages: Methodological aspects of the determination of the number of glucocorticoid receptors per cell

In the present study the human monoblast cell line U937 has been used as a model to study the function of human mononuclear phagocytes in asthma. The kinetics of the production of eicosanoids and cytokines, which are thought to play a role in the pathogenesis of asthma, were studied. In addition, the effects of glucocorticosteroids were investigated, as these drugs are of great importance for the treatment of asthmatic patients. After stimulation with phorbol-12 myristate acetate (PMA) for 24 h, U937 cells were cultured in the absence or presence of lipopolysaccharide (LPS: 1 and 5 microg ml(-1)) and glucocorticosteroids (budesonide, fluticasone propionate and prednisolone: 10(-11), 10(-9) and 10(-7) M) for 96 h. The production of interleukin-1beta (IL-1beta), interleukin-6 (IL-6), prostaglandin E2 (PGE2) and thromboxane B2 (TxB2) gradually increased in time after stimulation with LPS, whereas the transient production of tumor necrosis factor alpha (TNF-alpha) reached its maximum between 6 and 12 h. Interferon-gamma (IFN-gamma), interleukin-10 (IL-10) and leukotriene B4 (LTB4) were not detectable. All three glucocorticosteroids (budesonide, fluticasone propionate and prednisolone) completely inhibited the production of both eicosanoids and cytokines. The production of eicosanoids was more sensitive to these glucocorticoids than the production of cytokines. The observed differences in the kinetics of the production of eicosanoids and cytokines stress the importance of time course experiments in studies on the effect of drugs on mononuclear cells.

show abstract

Modulation of glucocorticoid receptor expression in human bronchial epithelial cell lines by IL-1 beta, TNF-alpha and LPS

Verheggen¹,

Hal²,

Adriaansen-Soeting³

et al. 1996

Eur Respir J

View full text Add to dashboard Cite

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

show abstract

scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.

Contact Info

hi@scite.ai

10624 S. Eastern Ave., Ste. A-614

Henderson, NV 89052, USA

Blog Terms and Conditions API Terms Privacy Policy Contact Cookie Preferences Do Not Sell or Share My Personal Information

Made with 💙 for researchers

Part of the Research Solutions Family.

Glucocorticoid receptors in alveolar macrophages: Methodological aspects of the determination of the number of glucocorticoid receptors per cell

Cited by 3 publications

References 4 publications

Multiple sclerosis: some possible therapeutic opportunities

Multiple sclerosis: some possible therapeutic opportunities

Time Dependent Production of Cytokines and Eicosanoids by Human Monocytic Leukaemia U937 Cells; Effects of Glucocorticosteroids

Modulation of glucocorticoid receptor expression in human bronchial epithelial cell lines by IL-1 beta, TNF-alpha and LPS

Contact Info

Product

Resources

About