BACKGROUND: CCAAT/enhancer-binding proteins (C/EBPs) control cell proliferation; lack of C/EBPalpha correlates with increased proliferation of bronchial smooth muscle cells (BSMCs) of asthmatic patients. OBJECTIVE: We sought to assess disease-specific expression of C/EBPalpha, 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/EBPalpha, 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/EBPalpha, beta, delta, and epsilon, which were upregulated by serum (5%). Budesonide completely inhibited C/EBPalpha and beta expression; formoterol increased C/EBPalpha expression (2-fold). C/EBPdelta and epsilon expression were not affected by the drugs. The asthmatic group did not appropriately express C/EBPalpha. Basal levels of C/EBPbeta, delta, and epsilon were upregulated by serum (5%). Budesonide and formoterol increased C/EBPbeta levels (3.4-fold and 2.5-fold, respectively), leaving C/EBPalpha, delta, and epsilon levels unaffected. The COPD group normally expressed C/EBPalpha, beta, and epsilon, which were upregulated by serum treatment (5%). Basal levels of C/EBPdelta were downregulated by serum in 7 of 10 BSMC lines. Budesonide inhibited C/EBPalpha and beta expression, upregulated C/EBPdelta (3.2-fold), and had no effect on C/EBPepsilon. Formoterol upregulated C/EBPalpha expression (3-fold) but not the other C/EBPs. Protein analysis and electrophoretic mobility shift assay confirmed the disease-specific expression pattern of C/EBPalpha in asthmatic patients and C/EBPdelta 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.
BACKGROUND: CCAAT/enhancer-binding proteins (C/EBPs) control cell proliferation; lack of C/EBPalpha correlates with increased proliferation of bronchial smooth muscle cells (BSMCs) of asthmatic patients. OBJECTIVE: We sought to assess disease-specific expression of C/EBPalpha, 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/EBPalpha, 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/EBPalpha, beta, delta, and epsilon, which were upregulated by serum (5%). Budesonide completely inhibited C/EBPalpha and beta expression; formoterol increased C/EBPalpha expression (2-fold). C/EBPdelta and epsilon expression were not affected by the drugs. The asthmatic group did not appropriately express C/EBPalpha. Basal levels of C/EBPbeta, delta, and epsilon were upregulated by serum (5%). Budesonide and formoterol increased C/EBPbeta levels (3.4-fold and 2.5-fold, respectively), leaving C/EBPalpha, delta, and epsilon levels unaffected. The COPD group normally expressed C/EBPalpha, beta, and epsilon, which were upregulated by serum treatment (5%). Basal levels of C/EBPdelta were downregulated by serum in 7 of 10 BSMC lines. Budesonide inhibited C/EBPalpha and beta expression, upregulated C/EBPdelta (3.2-fold), and had no effect on C/EBPepsilon. Formoterol upregulated C/EBPalpha expression (3-fold) but not the other C/EBPs. Protein analysis and electrophoretic mobility shift assay confirmed the disease-specific expression pattern of C/EBPalpha in asthmatic patients and C/EBPdelta 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.
Authors: Berran Yucesoy; Kenneth M Kaufman; Zana L Lummus; Matthew T Weirauch; Ge Zhang; André Cartier; Louis-Philippe Boulet; Joaquin Sastre; Santiago Quirce; Susan M Tarlo; Maria-Jesus Cruz; Xavier Munoz; John B Harley; David I Bernstein Journal: Toxicol Sci Date: 2015-04-26 Impact factor: 4.849
Authors: Elliot Israel; Jessica Lasky-Su; Amy Markezich; Amy Damask; Stanley J Szefler; Brooke Schuemann; Barbara Klanderman; Jody Sylvia; Shamsah Kazani; Rongling Wu; Fernando Martinez; Homer A Boushey; Vernon M Chinchilli; Dave Mauger; Scott T Weiss; Kelan G Tantisira Journal: Am J Respir Crit Care Med Date: 2015-03-01 Impact factor: 30.528
Authors: Laura Keglowich; Michael Roth; Maria Philippova; Thérèse Resink; Gavin Tjin; Brian Oliver; Didier Lardinois; Sophie Dessus-Babus; Reinoud Gosens; Katrin Hostettler Haack; Michael Tamm; Peter Borger Journal: PLoS One Date: 2013-12-05 Impact factor: 3.240