Biologic Effects of Inhaled Diesel Exhaust in Young and Old Mice: a Pilot Project

Project Details

Description

Exposure to particulate matter (PM) has been associated with increases in cardiopulmonary morbidity and mortality, with elderly people particularly susceptible. However, biologic pathways that might explain why the elderly are more susceptible than younger people to the effects of PM have not been examined extensively. Investigators propose a study to explore possible differences in the responses of young and old mice exposed to diesel exhaust. The investigators seek to evaluate the hypothesis that the increased susceptibility of elderly animals to PM results from impairment of the capacity of lung cells — alveolar macrophages, specifically — to produce the cytokine tumor necrosis factor a (TNF-a), as compared with lung-cell production of TNF-a by young animals. Laskin and colleagues reasoned that although TNF-a is pro-inflammatory — that is, it plays a central role in the induction of oxidative stress (a pathway emerging as a plausible mechanism to explain the adverse effects of exposure to PM) and inflammatory responses — TNF-a - is also thought to induce protective, antioxidant defenses and tissue-repair mechanisms, and thus it may play a role in limiting the extent of inflammatory responses and injury. The investigators objective is to test this hypothesis by comparing the production of TNF-a, other markers of the inflammatory response, and molecules involved in antioxidant defenses in young and elderly mice exposed to diesel exhaust emissions, a component of PM found in urban air.
StatusFinished
Effective start/end date4/1/103/31/15

Funding

  • U.S. Environmental Protection Agency

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