Decreased CCAAT/enhancer binding protein transcription factor activity in chronic bronchitis and COPD.

Abstract

BACKGROUND: CCAAT/enhancer binding proteins (C/EBPs) are key regulators of cell differentiation and linked processes such as proliferation, apoptosis, and gene expression in several organs. C/EBPs are also central for inflammatory responses and infectious defenses, but so far little is known of their role in lung diseases. Chronic bronchitis (CB) and COPD are common smoking-associated lung diseases involving the airway epithelium. METHODS: Gelshifts were used to study C/EBP transcription factor activity in airway epithelial cells obtained by bronchial brush biopsy in four groups: healthy never-smokers (n = 10), asymptomatic smokers (n = 7), and smokers with CB and recurrent infectious exacerbations without COPD (n = 23) and with COPD (n = 13). RESULTS: C/EBP-binding activity was increased 4.6-fold in airway epithelial cells of healthy smokers compared with never-smokers. In contrast, C/EBP binding activity was not increased in the epithelium of smokers with CB or COPD. C/EBP-beta was the dominant C/EBP in the airway epithelium in all groups. CONCLUSIONS: We hypothesize that this lack of increase in C/EBP-beta activity renders the epithelium incompetent of efficient regeneration and more sensitive to infection, suggesting a previously unknown role for C/EBPs in the pathogenesis of CB and COPD.