International Journal of Chronic Obstructive Pulmonary Disease
- About Dovepress
Open access peer-reviewed scientific and medical journals.
- Open Access
Dove Medical Press is now a member of the Open Access Initiative
- An Author's Guide
A guide to help authors get their paper published.
Support Open Access and Dove Press
Promotional Article Monitoring - further details
- Favored Author Program
Real benefits for authors, including fast-track processing of papers.
Induction of the unfolded protein response by cigarette smoke is primarily an activating transcription factor 4-C/EBP homologous protein mediated process
(5987) Total Article Views
Authors: Geraghty P, Wallace A, D'Armiento J
Published Date June 2011 Volume 2011:6 Pages 309 - 319 Patrick Geraghty, Alison Wallace, Jeanine M D'Armiento
Department of Medicine, Divisions of Molecular and Pulmonary Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA
Purpose: Cigarette smoke is the major risk factor associated with the development of chronic obstructive pulmonary disease (COPD). Recent studies propose a link between endoplasmic reticulum (ER) stress and emphysema, demonstrated by increased ER stress markers under smoking conditions. Here, we investigate whether cigarette smoke-induced ER stress is cell specific and correlates with acute and chronic cigarette smoke exposure.
Methods: Gene and protein expression changes in human primary lung cell cultures following cigarette smoke extract (CSE) exposure were monitored by qPCR and Western blot analysis. Mice and guinea pigs were exposed to cigarette smoke and ER stress markers examined in whole lung homogenates. Inflammatory cells from the bronchoalveolar lavage fluid of 10 days smoke exposed mice were also examined.
Results: Cigarette smoke induced a trend increase in the ER stress response through an activating transcription factor 4 (ATF4) mediated induction of C/EBP homologous protein (CHOP) in primary small airway epithelial cells. Bronchial epithelial cells and macrophages responded similarly to CSE. Wild-type mice and guinea pigs exposed to acute levels of cigarette smoke exhibited increased levels of CHOP but not at significant levels. However, after long-term chronic cigarette smoke exposure, CHOP expression was reduced. Interestingly, inflammatory cells from smoke exposed mice had a significant increase in CHOP/ATF4 expression.
Conclusion: A trend increase in CHOP levels appear in multiple human lung cell types following acute cigarette smoke exposure in vitro. In vivo, inflammatory cells, predominately macrophages, demonstrate significant cigarette smoke-induced ER stress. Early induction of CHOP in cigarette smoke may play a pivotal role in early induction of lung disease, however in vivo long-term cigarette smoke exposure exhibited a reduction in the ER stress response.
Keywords: COPD, ER stress, cigarette smoke, CHOP
Cannotea Citeulike Del.icio.us Facebook LinkedIn Twitter
Readers of this article also read:
- Journal Indexing
See where all the Dove Press journals are indexed.
"You do a tremendous job!!" Ruben Restrepo, University of Texas Health Science Center, San Antonio.
- Clinical effectiveness of the Respimat® inhaler device in managing chronic obstructive pulmonary disease: evidence when compared with other handheld inhaler devices
- Chronic obstructive pulmonary disease as an independent risk factor for cardiovascular morbidity
- The pathophysiology of bronchiectasis
- Exacerbation rate, health status and mortality in COPD – a review of potential interventions