title: Mycoplasma pneumoniae infection and environmental tobacco smoke inhibit lung glutathione adaptive responses and increase oxidative stress.
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.
authors.affiliation: University of Colorado Health Sciences Center, Denver, Colorado 80206, USA..
authors.forename: Chirag
authors.initials: C
authors.lastname: Kariya
authors.forename: Hong Wei
authors.initials: HW
authors.lastname: Chu
authors.forename: Jie
authors.initials: J
authors.lastname: Huang
authors.forename: Heather
authors.initials: H
authors.lastname: Leitner
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Martin
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Day
mesh_terms: D000818:Animals; D001826:Body Fluids / Q000737:chemistry; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D004847:Epithelial Cells / Q000737:chemistry / Q000382:microbiology; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D008168:Lung / Q000737:chemistry / Q000187:drug effects / Q000382:microbiology / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009177:Mycoplasma pneumoniae / Q000502:physiology*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011019:Pneumonia, Mycoplasma / Q000382:microbiology; D020545:Respiratory Mucosa / Q000737:chemistry; D012906:Smoke
chemical_list: D012906:Smoke; D004247:DNA; D005978:Glutathione