Compartmentalization of anti-oxidant and anti-inflammatory gene expression in current and former smokers with COPD
Abstract Background Patients with chronic obstructive pulmonary disease (COPD) have high oxidative stress associated with the severity of the disease. Nuclear factor erythroid-2 related factor 2 (Nrf2)-directed stress response plays a critical role in the protection of lung cells to oxidative stress...
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doaj-39e20bf8927e411b898613bd7419fbb52020-11-25T02:58:47ZengBMCRespiratory Research1465-993X2019-08-012011910.1186/s12931-019-1164-1Compartmentalization of anti-oxidant and anti-inflammatory gene expression in current and former smokers with COPDVenkataramana K. Sidhaye0Janet T. Holbrook1Alyce Burke2Kuladeep R. Sudini3Sanjay Sethi4Gerard J. Criner5Jed W. Fahey6Charles S. Berenson7Michael R. Jacobs8Rajesh Thimmulappa9Robert A. Wise10Shyam Biswal11School of Medicine, Johns Hopkins UniversityJohns Hopkins Bloomberg School of Public HealthJohns Hopkins Bloomberg School of Public HealthJohns Hopkins Bloomberg School of Public HealthUniversity at Buffalo, SUNY, and VA WNY Healthcare SystemLewis Katz School of Medicine at Temple UniversitySchool of Medicine, Johns Hopkins UniversityUniversity at Buffalo, SUNY, and VA WNY Healthcare SystemLewis Katz School of Medicine at Temple UniversityJSS Medical College, JSS Academy of Higher Education & ResearchSchool of Medicine, Johns Hopkins UniversityJohns Hopkins Bloomberg School of Public HealthAbstract Background Patients with chronic obstructive pulmonary disease (COPD) have high oxidative stress associated with the severity of the disease. Nuclear factor erythroid-2 related factor 2 (Nrf2)-directed stress response plays a critical role in the protection of lung cells to oxidative stress by upregulating antioxidant genes in response to tobacco smoke. There is a critical gap in our knowledge about Nrf-2 regulated genes in active smokers and former-smokers with COPD in different cell types from of lungs and surrogate peripheral tissues. Methods We compared the expression of Nrf2 and six of its target genes in alveolar macrophages, nasal, and bronchial epithelium and peripheral blood mononuclear cells (PBMCs) in current and former smokers with COPD. We compared cell-type specific of Nrf2 and its target genes as well as markers of oxidative and inflammatory stress. Results We enrolled 89 patients; expression all Nrf2 target gene measured were significantly higher in the bronchial epithelium from smokers compared to non-smokers. None were elevated in alveolar macrophages and only one was elevated in each of the other compartments. Conclusion Bronchial epithelium is the most responsive tissue for transcriptional activation of Nrf2 target genes in active smokers compared to former-smokers with COPD that correlated with oxidative stress and inflammatory markers. There were no consistent trends in gene expression in other cell types tested. Trial registration Clinicaltrials.gov: NCT01335971.http://link.springer.com/article/10.1186/s12931-019-1164-1COPDSmokersOxidative stressEpithelial cellsMacrophagesNrf2 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Venkataramana K. Sidhaye Janet T. Holbrook Alyce Burke Kuladeep R. Sudini Sanjay Sethi Gerard J. Criner Jed W. Fahey Charles S. Berenson Michael R. Jacobs Rajesh Thimmulappa Robert A. Wise Shyam Biswal |
spellingShingle |
Venkataramana K. Sidhaye Janet T. Holbrook Alyce Burke Kuladeep R. Sudini Sanjay Sethi Gerard J. Criner Jed W. Fahey Charles S. Berenson Michael R. Jacobs Rajesh Thimmulappa Robert A. Wise Shyam Biswal Compartmentalization of anti-oxidant and anti-inflammatory gene expression in current and former smokers with COPD Respiratory Research COPD Smokers Oxidative stress Epithelial cells Macrophages Nrf2 |
author_facet |
Venkataramana K. Sidhaye Janet T. Holbrook Alyce Burke Kuladeep R. Sudini Sanjay Sethi Gerard J. Criner Jed W. Fahey Charles S. Berenson Michael R. Jacobs Rajesh Thimmulappa Robert A. Wise Shyam Biswal |
author_sort |
Venkataramana K. Sidhaye |
title |
Compartmentalization of anti-oxidant and anti-inflammatory gene expression in current and former smokers with COPD |
title_short |
Compartmentalization of anti-oxidant and anti-inflammatory gene expression in current and former smokers with COPD |
title_full |
Compartmentalization of anti-oxidant and anti-inflammatory gene expression in current and former smokers with COPD |
title_fullStr |
Compartmentalization of anti-oxidant and anti-inflammatory gene expression in current and former smokers with COPD |
title_full_unstemmed |
Compartmentalization of anti-oxidant and anti-inflammatory gene expression in current and former smokers with COPD |
title_sort |
compartmentalization of anti-oxidant and anti-inflammatory gene expression in current and former smokers with copd |
publisher |
BMC |
series |
Respiratory Research |
issn |
1465-993X |
publishDate |
2019-08-01 |
description |
Abstract Background Patients with chronic obstructive pulmonary disease (COPD) have high oxidative stress associated with the severity of the disease. Nuclear factor erythroid-2 related factor 2 (Nrf2)-directed stress response plays a critical role in the protection of lung cells to oxidative stress by upregulating antioxidant genes in response to tobacco smoke. There is a critical gap in our knowledge about Nrf-2 regulated genes in active smokers and former-smokers with COPD in different cell types from of lungs and surrogate peripheral tissues. Methods We compared the expression of Nrf2 and six of its target genes in alveolar macrophages, nasal, and bronchial epithelium and peripheral blood mononuclear cells (PBMCs) in current and former smokers with COPD. We compared cell-type specific of Nrf2 and its target genes as well as markers of oxidative and inflammatory stress. Results We enrolled 89 patients; expression all Nrf2 target gene measured were significantly higher in the bronchial epithelium from smokers compared to non-smokers. None were elevated in alveolar macrophages and only one was elevated in each of the other compartments. Conclusion Bronchial epithelium is the most responsive tissue for transcriptional activation of Nrf2 target genes in active smokers compared to former-smokers with COPD that correlated with oxidative stress and inflammatory markers. There were no consistent trends in gene expression in other cell types tested. Trial registration Clinicaltrials.gov: NCT01335971. |
topic |
COPD Smokers Oxidative stress Epithelial cells Macrophages Nrf2 |
url |
http://link.springer.com/article/10.1186/s12931-019-1164-1 |
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