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Infect. Immun. doi:10.1128/IAI.00136-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Mycoplasma Infection and Environmental Tobacco Smoke Inhibit Lung Glutathione Adaptive Responses and Increase Oxidative Stress

Departments of Medicine, Immunology, and Pharmaceutical Sciences, University of Colorado Health Sciences Center and Department of Medicine, National Jewish Medical & Research Center, Denver, Colorado, USA

^* To whom correspondence should be addressed. Email: dayb{at}njc.org.

	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 (Mp) can exacerbate airway inflammation and oxidative stress. The present studies examined whether Mp infections synergize with ETS to disrupt lung GSH adaptive responses. Mice were exposed separately and in combination to ETS and Mp for 16 weeks. ETS exposure resulted in a doubling of ELF GSH levels, which was blocked in the Mp exposed mice. In addition, the ETS + Mp 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 (CSE) and Mp for 48 hours had elevated apical levels of GSH as compared to control cells and these increases were blocked by Mp and were also associated with increased cellular DNA oxidation. Further studies showed that Mp exposure blocked ETS-induced increases in glutathione reductase (GR), an enzyme that recycles GSSG back to GSH, both in vitro and in vivo. These studies suggest Mp infection synergizes with ETS and suppresses the lung's ability to response appropriately to environmental challenges leading to enhanced oxidative stress.