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.
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.
Authors: James Y Lindsey; Koustav Ganguly; David M Brass; Zhuowei Li; Erin N Potts; Simone Degan; Huaiyong Chen; Brian Brockway; Soman N Abraham; Annerose Berndt; Barry R Stripp; W Michael Foster; George D Leikauf; Holger Schulz; John W Hollingsworth Journal: Am J Respir Crit Care Med Date: 2011-03-11 Impact factor: 21.405
Authors: Maciej Cabanski; Brett Fields; Stephanie Boue; Natalia Boukharov; Hector DeLeon; Natalie Dror; Marcel Geertz; Emmanuel Guedj; Anita Iskandar; Ulrike Kogel; Celine Merg; Michael J Peck; Carine Poussin; Walter K Schlage; Marja Talikka; Nikolai V Ivanov; Julia Hoeng; Manuel C Peitsch Journal: Inflamm Res Date: 2015-05-12 Impact factor: 4.575
Authors: Jiyoun Yeo; Diego A Morales; Tian Chen; Erin L Crawford; Xiaolu Zhang; Thomas M Blomquist; Albert M Levin; Pierre P Massion; Douglas A Arenberg; David E Midthun; Peter J Mazzone; Steven D Nathan; Ronald J Wainz; Patrick Nana-Sinkam; Paige F S Willey; Taylor J Arend; Karanbir Padda; Shuhao Qiu; Alexei Federov; Dawn-Alita R Hernandez; Jeffrey R Hammersley; Youngsook Yoon; Fadi Safi; Sadik A Khuder; James C Willey Journal: BMC Pulm Med Date: 2018-03-05 Impact factor: 3.317