Dysfunctional Interaction of C/EBPα and the Glucocorticoid Receptor in Asthmatic Bronchial Smooth-Muscle Cells

• Published in: The New England journal of medicine Vol. 351; no. 6; pp. 560 - 574
• Main Authors: Roth, Michael, Johnson, Peter R.A, Borger, Peter, Bihl, Michel P, Rüdiger, Jochen J, King, Gregory G, Ge, Qi, Hostettler, Katrin, Burgess, Janette K, Black, Judith L, Tamm, Michael
• Format: Journal Article
• Language: English
• Published: Boston, MA Massachusetts Medical Society 05.08.2004
• Subjects: Biological and medical sciences; Chronic obstructive pulmonary disease, asthma; General aspects; Medical sciences; Pneumology; Medicine; Lung disease; Respiratory disease; Interaction; Bronchus disease; Smooth muscle; Obstructive pulmonary disease; Glucocorticoid; Asthma; Myocyte; Biological receptor; C/EBP transcription factor
• ISSN: 0028-4793; 1533-4406
• DOI: 10.1056/NEJMoa021660

Normally, the growth of airway smooth-muscle cells is kept in check by the antiproliferative effects of glucocorticoids acting in concert with the glucocorticoid receptor and CCAAT/enhancer binding protein α (C/EBPα). These investigators show that airway smooth muscle from patients with asthma has a selective deficiency of C/EBPα, thus obviating the antiproliferative effects of glucocorticoids. A selective deficiency of CCAAT/ enhancer binding protein α in airway smooth muscle from patients with asthma. Asthma is characterized pathologically by an increased mass of bronchial smooth muscle, 1 , 2 apparently as a result of the enhanced proliferation of bronchial smooth-muscle cells. 3 , 4 Bronchial smooth-muscle cells are thus considered a major target for antiasthma treatments such as glucocorticoids. 5 Glucocorticoids down-regulate the secretion of several inflammatory cytokines by various types of cells resident in the human lung, 6 – 9 and this process is thought to be mediated by the ligand-activated glucocorticoid receptor. 9 – 11 On activation, the glucocorticoid receptor migrates to the nucleus, where it binds to its specific DNA consensus sequence, the glucocorticoid-responsive element, 9 – 11 or interacts with other . . .