Disease-specific expression and regulation of CCAAT/enhancer-binding proteins in asthma and chronic obstructive pulmonary disease

Background: CCAAT/enhancer-binding proteins (C/EBPs) control cell proliferation; lack of C/EBP alpha correlates with increased proliferation of bronchial smooth muscle cells (BSMCs) of asthmatic patients. Objective: We sought to assess disease-specific expression of C/EBP alpha, beta, delta, and epsilon and the effects of budesonide (10(-8) mol/L) and formoterol (10(-8) mol/L). Methods: Expression and function of C/EBP alpha, beta, delta, and epsilon BSMCs of control subjects (n = 9), asthmatic patients (n = 12), and patients with chronic obstructive pulmonary disease (COPD; n = 10) were determined. Results: The control group expressed C/EBP alpha, beta, delta, and epsilon, which were upregulated by serum (5%). Budesonide completely inhibited C/EBP alpha and beta expression; formoterol increased C/EBP alpha expression (2-fold). C/EBP delta and epsilon expression were not affected by the drugs. The asthmatic group did not appropriately express C/EBP alpha. Basal levels of C/EBP beta, delta, and epsilon were upregulated by serum (5%). Budesonide and formoterol increased C/EBP beta levels (3.4-fold and 2.5-fold, respectively), leaving C/EBP alpha, delta, and epsilon levels unaffected. The COPD group normally expressed C/EBP alpha, beta, and epsilon, which were upregulated by serum treatment (5%). Basal levels of C/EBP,5 were downregulated by serum in 7 of 10 BSMC lines. Budesonide inhibited C/EBPa and P expression, upregulated C/EBP delta (3.2-fold), and had no effect on C/EBP epsilon. Formoterol upregulated C/EBP alpha expression (3-fold) but not the other C/EBPs. Protein analysis and electrophoretic mobility shift assay confirmed the disease-specific expression pattern of C/EBP alpha in asthmatic patients and C/EBP delta in patients with COPD. Conclusions: The expression and regulation of C/EBPs in BSMCs of asthmatic patients and patients with COPD seems disease specific. Budesonide and formoterol modulate C/EBP expression in a drug- and disease-specific pattern. Clinical implications: The data could provide a method to discriminate between asthma and COPD at an early disease stage.