The role of bronchial epithelial cell apoptosis in the pathogenesis of COPD
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There is an increased airway inflammation in the pathogenesis of chronic obstructive pulmonary disease (COPD), and it has been suggested that there may also be problem in the apoptosis and renewal of cells. However, there are limited human airway cell studies, in particular those from larger airways such as bronchi. We cultured primary human bronchial epithelial cells (HBECs) from bronchial explants of smokers (n = 6) without COPD and smokers with COPD (n = 8). Apoptosis was studied by fluorescence activated cell sorting. qRT-PCR was used to assess mRNA expression for proteins involving apoptosis including p21CIP1/WAF1, p53, caspase-8 and caspase-9. Although there was no difference in the rate of viable cells between cells from smokers and COPDs, the level of early apoptotic cells was significantly increased in COPD cells [mean ± standard error of mean (SEM) = 4.86 ± 3.2 %, p = 0.015] as compared to smokers (mean ± SEM = 2.71 ± 1.62 %). In contrast, the rate of late apoptotic cells was significantly decreased in COPD cells (mean ± SEM = 9.82 ± 5.71 %) comparing to smokers (mean ± SEM = 15.21 ± 5.08 %, p = 0.003). Although expression of mRNA for p21CIP1/WAF1 and caspase-9 was similar in both groups, p53 and caspase-8 mRNA expression was significantly greater in COPD cells. These findings suggest that HBEC apoptosis is increased in COPD, and that this involves p53 and caspase-8 pathways.
KeywordsApoptosis Caspases COPD Primary bronchial epithelial cells p21 p53
This study is funded by The Research Fund of Gaziantep University with the Grant No.: TF.11.32.
- 1.Goldcopd.org. Global strategy for the diagnosis, management, and prevention of COPD [updated 2013] www.goldcopd.org/uploads/users/files/GOLD_Report_2013_Feb20.pdf
- 16.Bayram H, Devalia JL, Khair OA, Abdelaziz MM, Sapsford RJ, Sagai M, Davies RJ (1998) Comparison of ciliary activity and inflammatory mediator release from bronchial epithelial cells of nonatopic nonasthmatic subjects and atopic asthmatic patients and the effect of diesel exhaust particles in vitro. J Allergy Clin Immunol 102(5):771–782CrossRefPubMedGoogle Scholar
- 22.Uhal BD, Joshi I, Hughes WF, Ramos C, Pardo A, Selman M (1998) Alveolar epithelial cell death adjacent to underlying myofibroblasts in advanced fibrotic human lung. Am J Physiol 275(6 Pt 1):1192–1199Google Scholar
- 28.Slebos DJ, Ryter SW, van der Toorn M, Liu F, Guo F, Baty CJ, Karlsson JM, Watkins SC, Kim HP, Wang X, Lee JS, Postma DS, Kauffman HF, Choi AM (2007) Mitochondrial localization and function of heme oxygenase-1 in cigarette smoke-induced cell death. Am J Respir Cell Mol Biol 36(4):409–417. doi: 10.1165/rcmb.2006-0214OC PubMedCentralCrossRefPubMedGoogle Scholar
- 29.Siganaki M, Koutsopoulos AV, Neofytou E, Vlachaki E, Psarrou M, Soulitzis N, Pentilas N, Schiza S, Siafakas NM, Tzortzaki EG (2010) Deregulation of apoptosis mediators’ p53 and bcl2 in lung tissue of COPD patients. Respir Res 11:46. doi: 10.1186/1465-9921-11-46 PubMedCentralCrossRefPubMedGoogle Scholar
- 30.Chiappara G, Gjomarkaj M, Virzi A, Sciarrino S, Ferraro M, Bruno A, Montalbano AM, Vitulo P, Minervini MI, Pipitone L, Pace E (2013) The role of p21 Waf1/Cip1 in large airway epithelium in smokers with and without COPD. Biochim Biophys Acta 1832(10):1473–1481. doi: 10.1016/j.bbadis.2013.04.022 CrossRefPubMedGoogle Scholar