دورية أكاديمية

Long-term smoking alters abundance of over half of the proteome in bronchoalveolar lavage cell in smokers with normal spirometry, with effects on molecular pathways associated with COPD

التفاصيل البيبلوغرافية
العنوان: Long-term smoking alters abundance of over half of the proteome in bronchoalveolar lavage cell in smokers with normal spirometry, with effects on molecular pathways associated with COPD
المؤلفون: Mingxing Yang, Maxie Kohler, Tina Heyder, Helena Forsslund, Hilde K. Garberg, Reza Karimi, Johan Grunewald, Frode S. Berven, C. Magnus Sköld, Åsa M. Wheelock
المصدر: Respiratory Research, Vol 19, Iss 1, Pp 1-11 (2018)
بيانات النشر: BMC, 2018.
سنة النشر: 2018
المجموعة: LCC:Diseases of the respiratory system
مصطلحات موضوعية: Smoking, Inflammation, Proteomics, COPD, Bronchoalveolar lavage, Diseases of the respiratory system, RC705-779
الوصف: Abstract Background Smoking represents a significant risk factor for many chronic inflammatory diseases, including chronic obstructive pulmonary disease (COPD). Methods To identify dysregulation of specific proteins and pathways in bronchoalveolar lavage (BAL) cells associated with smoking, isobaric tags for relative and absolute quantitation (iTRAQ)-based shotgun proteomics analyses were performed on BAL cells from healthy never-smokers and smokers with normal lung function from the Karolinska COSMIC cohort. Multivariate statistical modeling, multivariate correlations with clinical data, and pathway enrichment analysis were performed. Results Smoking exerted a significant impact on the BAL cell proteome, with more than 500 proteins representing 15 molecular pathways altered due to smoking. The majority of these alterations occurred in a gender-independent manner. The phagosomal- and leukocyte trans endothelial migration (LTM) pathways significantly correlated with FEV1/FVC as well as the percentage of CD8+ T-cells and CD8+CD69+ T-cells in smokers. The correlations to clinical parameters in healthy never-smokers were minor. Conclusion The significant correlations of proteins in the phagosome- and LTM pathways with activated cytotoxic T-cells (CD69+) and the level of airway obstruction (FEV1/FVC) in smokers, both hallmarks of COPD, suggests that these two pathways may play a role in the molecular events preceding the development of COPD in susceptible smokers. Both pathways were found to be further dysregulated in COPD patients from the same cohort, thereby providing further support to this hypothesis. Given that not all smokers develop COPD in spite of decades of smoking, it is also plausible that some of the molecular pathways associated with response to smoking exert protective mechanisms to smoking-related pathologies in resilient individuals. Trial registration ClinicalTrials.gov identifier NCT02627872; Retrospectively registered on December 9, 2015.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1465-993X
Relation: http://link.springer.com/article/10.1186/s12931-017-0695-6; https://doaj.org/toc/1465-993X
DOI: 10.1186/s12931-017-0695-6
URL الوصول: https://doaj.org/article/180a839f3dd64da8b43b11f8666dc083
رقم الأكسشن: edsdoj.180a839f3dd64da8b43b11f8666dc083
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:1465993X
DOI:10.1186/s12931-017-0695-6