Journal Article

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

Criner, Gerard J., Sudini, Kuladeep R., Sidhaye, Venkataramana K., Biswal, Shyam, Burke, Alyce, Sethi, Sanjay, Berenson, Charles S., Holbrook, Janet T., Thimmulappa, Rajesh, Fahey, Jed W., Wise, Robert A., Jacobs, Michael R.

2019

Overview

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.

• Publisher: BioMed Central,BioMed Central Ltd,Nature Publishing Group,BMC
• Subject: Aged / Alveoli / Antioxidants / Antioxidants - metabolism / Bronchi - metabolism / Cellular stress response / Chronic obstructive lung disease / Chronic obstructive pulmonary disease / Comparative analysis / Complications and side effects / COPD / Double-Blind Method / Epithelial cells / Epithelium / Epithelium - metabolism / Female / GA-binding protein / Gene Expression / Genes / Genetic aspects / Health aspects / Humans / Inflammation / Inflammation - genetics / Inflammation - metabolism / Isothiocyanates - therapeutic use / Leukocytes (mononuclear) / Lung diseases / Lungs / Macrophages / Macrophages - metabolism / Male / Markers / Medicine / Medicine & Public Health / Middle Aged / Monocytes - metabolism / NF-E2-Related Factor 2 - biosynthesis / NF-E2-Related Factor 2 - genetics / Nrf2 / NRF2 protein / Obstructive lung disease / Oxidative stress / Oxidative Stress - genetics / Oxidizing agents / Peripheral blood mononuclear cells / Pneumology/Respiratory System / Pulmonary Disease, Chronic Obstructive - genetics / Pulmonary Disease, Chronic Obstructive - metabolism / Smoke / Smokers / Smoking / Smoking - genetics / Smoking - metabolism / Smoking Cessation / Sulfoxides / Tobacco / Transcription activation / Transcriptional Activation