Compartmentalization of anti-oxidant and anti-inflammatory gene expression in current and former smokers with COPD

Venkataramana Sidhaye, Janet Teresa 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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number190
JournalRespiratory research
Volume20
Issue number1
DOIs
StatePublished - Aug 20 2019

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Oxidants
Chronic Obstructive Pulmonary Disease
Anti-Inflammatory Agents
Gene Expression
Oxidative Stress
Genes
Alveolar Macrophages
Epithelium
Lung
Cytoprotection
Nasal Mucosa
Smoke
Transcriptional Activation
Tobacco
Blood Cells
Antioxidants

Keywords

  • COPD
  • Epithelial cells
  • Macrophages
  • Nrf2
  • Oxidative stress
  • Smokers

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Compartmentalization of anti-oxidant and anti-inflammatory gene expression in current and former smokers with COPD. / Sidhaye, Venkataramana; Holbrook, Janet Teresa; Burke, Alyce; Sudini, Kuladeep R.; Sethi, Sanjay; Criner, Gerard J.; Fahey, Jed W; Berenson, Charles S.; Jacobs, Michael R.; Thimmulappa, Rajesh; Wise, Robert A; Biswal, Shyam.

In: Respiratory research, Vol. 20, No. 1, 190, 20.08.2019.

Research output: Contribution to journalArticle

Sidhaye, Venkataramana ; Holbrook, Janet Teresa ; Burke, Alyce ; Sudini, Kuladeep R. ; Sethi, Sanjay ; Criner, Gerard J. ; Fahey, Jed W ; Berenson, Charles S. ; Jacobs, Michael R. ; Thimmulappa, Rajesh ; Wise, Robert A ; Biswal, Shyam. / Compartmentalization of anti-oxidant and anti-inflammatory gene expression in current and former smokers with COPD. In: Respiratory research. 2019 ; Vol. 20, No. 1.
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AU - Burke, Alyce

AU - Sudini, Kuladeep R.

AU - Sethi, Sanjay

AU - Criner, Gerard J.

AU - Fahey, Jed W

AU - Berenson, Charles S.

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AU - Thimmulappa, Rajesh

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AU - Biswal, Shyam

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AB - 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.

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