Mycoplasma pneumoniae Infection and Environmental Tobacco Smoke Inhibit Lung Glutathione Adaptive Responses and Increase Oxidative Stress
- 1 October 2008
- journal article
- Published by American Society for Microbiology in Infection and Immunity
- Vol. 76 (10), 4455-4462
- https://doi.org/10.1128/iai.00136-08
Abstract
Chronic cigarette smoking evokes a lung glutathione (GSH) adaptive response that results in elevated GSH levels in the lung epithelial lining fluid (ELF). Currently, little is known about how the lung regulates or maintains steady-state levels of ELF GSH. Pathogens such as Mycoplasma pneumoniae can exacerbate airway inflammation and oxidative stress. The present study examined whether M. pneumoniae infections synergize with environmental tobacco smoke (ETS) to disrupt lung GSH adaptive responses. Mice were exposed separately and in combination to ETS and M. pneumoniae for 16 weeks. ETS exposure resulted in a doubling of ELF GSH levels, which was blocked in the M. pneumoniae -exposed mice. In addition, the ETS-plus- M. pneumoniae -exposed mice had elevated levels of oxidized glutathione (GSSG), resulting in a dramatic change in the ELF redox state that corresponded with an increase in lung tissue DNA oxidation. Similar findings were observed in human lung epithelial cells in vitro. Cells exposed separately or in combination to cigarette smoke extract and M. pneumoniae for 48 h had elevated apical levels of GSH compared to control cells, and these increases were blocked by M. pneumoniae and were also associated with increased cellular DNA oxidation. Further studies showed that M. pneumoniae exposure blocked ETS-induced increases in GSH reductase, an enzyme that recycles GSSG back to GSH, both in vitro and in vivo. These studies suggest that M. pneumoniae infection synergizes with ETS and suppresses the lung's ability to respond appropriately to environmental challenges leading to enhanced oxidative stress.Keywords
This publication has 48 references indexed in Scilit:
- Glutathione Peroxidase 2, the Major Cigarette Smoke–Inducible Isoform of GPX in Lungs, Is Regulated by Nrf2American Journal of Respiratory Cell and Molecular Biology, 2006
- Mitochondrial Oxidative Stress in the Lungs of Cystic Fibrosis Transmembrane Conductance Regulator Protein Mutant MiceAmerican Journal of Respiratory Cell and Molecular Biology, 2006
- Active defense under oxidative stress. The antioxidant responsive elementBiochemistry (Moscow), 2006
- Oxidant and antioxidant balance in the airways and airway diseasesEuropean Journal of Pharmacology, 2006
- Role for Cystic Fibrosis Transmembrane Conductance Regulator Protein in a Glutathione Response to Bronchopulmonary Pseudomonas InfectionInfection and Immunity, 2004
- Dose-response relationship in tobacco-related cancers of bladder and lung: A biochemical interpretationInternational Journal of Cancer, 2003
- Infectious etiologies in acute exacerbation of COPDDiagnostic Microbiology and Infectious Disease, 2001
- Transcriptional Regulation of γ-Glutamylcysteine Synthetase-Heavy Subunit by Oxidants in Human Alveolar Epithelial CellsBiochemical and Biophysical Research Communications, 1996
- The effect of acute cigarette smoke inhalation on pulmonary and systemic cysteine and glutathione redox states in the ratToxicology, 1987
- Mycoplasmas as Agents of Human DiseaseNew England Journal of Medicine, 1981