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

Pulmonary Cell Research, Department of Research and Pneumology, Department of Internal Medicine, University Hospital Basel, Basel, Switzerland.
Journal of Allergy and Clinical Immunology (Impact Factor: 11.48). 02/2007; 119(1):98-105. DOI: 10.1016/j.jaci.2006.07.056
Source: PubMed


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.
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).
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.
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.
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.
The data could provide a method to discriminate between asthma and COPD at an early disease stage.

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Available from: Pieter Borger, Dec 06, 2015
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    • "It has been shown that bronchial smooth muscle cells (BSMC) isolated from asthma patients release more pro-inflammatory mediators than BSMC from control subjects [7-9]. These findings suggest that BSMC of asthma patients exhibit a hyper-reactive “primed” phenotype, which may be explained, at least in part, by an aberrant expression of the transcription regulator CCAAT/enhancer binding protein α (C/EBPα) [7,10-12]. "
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    • "Alternatively, lithium chloride has been shown to prevent the degradation of C/EBPα protein and might be tested as a candidate drug to counteract airway wall remodelling in asthma [210]. Similar strategies might be envisioned in the treatment of the remodeling processes in the lung of COPD patients, but with the focus on C/EBPδ [196]. "
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