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

EPA Grant Number: R834677C151
Subproject: this is subproject number 151 , established and managed by the Center Director under grant R834677
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).

Center: Health Effects Institute (2010 — 2015)
Center Director: Greenbaum, Daniel S.
Title: Biologic Effects of Inhaled Diesel Exhaust in Young and Old Mice: A Pilot Project
Investigators: Laskin, Deborah
Institution: Rutgers, The State University of New Jersey , Environmental and Occupational Health Sciences Institute , Health Effects Institute (HEI)
EPA Project Officer: Hunt, Sherri
Project Period: April 1, 2010 through March 31, 2015
RFA: Health Effects Institute (2010) RFA Text |  Recipients Lists
Research Category: Health Effects , Air Quality and Air Toxics , Air


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.


The investigators will assess the lungs of mice histologically immediately after and 24 hours after the end of exposure for qualitative changes in markers of inflammation (such as edema and numbers of macrophages and neutrophils) and expression of the manganese-dependent isoform of superoxide dismutase, an enzyme involved in antioxidant defenses. They will also measure messenger RNA (mRNA) and protein levels of TNF-a and several molecules associated with inflammation and injury in lung tissue and bronchoalveolar-lavage fluid. These molecules included interleukin-8 (a cytokine that recruits neutrophils into tissues in response to an inflammatory stimulus), interleukin-6 (an acute-phase protein, a component of the rapid systemic response to infectious or other agents), cyclooxygenase-2 (an enzyme that synthesizes prostaglandins, which are involved in inflammatory responses), and lipocalin 24p3 (another acute-phase protein). They will also measure levels of TNF-a in the blood.

Expected Results:

The investigators hypothesis is that TNF-a production will be shown to be impaired in old animals exposed to diesel exhaust. The investigators extend  their hypothesis to suggest that exposure to diesel exhaust may differentially affect molecules involved in inflammation and protective antioxidant pathways in young and old mice.

Supplemental Keywords:

Health Effects, Air Toxics, urban air toxics, indoor air, epidemiology, mobile-source air toxics,  exposure models, diesel exhaust, susceptibility

Relevant Websites: Exit

Main Center Abstract and Reports:

R834677    Health Effects Institute (2010 — 2015)

Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R834677C149 Development and Application of a Sensitive Method to Determine Concentrations of Acrolein and Other Carbonyls in Ambient Air
R834677C150 Mutagenicity of Stereochemical Configurations of 1,3-Butadiene Epoxy Metabolites in Human Cells
R834677C151 Biologic Effects of Inhaled Diesel Exhaust in Young and Old Mice: A Pilot Project
R834677C152 Evaluating Heterogeneity in Indoor and Outdoor Air Pollution Using Land-Use Regression and Constrained Factor Analysis
R834677C153 Improved Source Apportionment and Speciation of Low-Volume Particulate Matter Samples
R834677C155 The Impact of the Congestion Charging Scheme on Air Quality in London
R834677C156 Concentrations of Air Toxics in Motor Vehicle-Dominated Environments
R834677C158 Air Toxics Exposure from Vehicle Emissions at a U.S. Border Crossing: Buffalo Peace Bridge Study
R834677C159 Role of Neprilysin in Airway Inflammation Induced by Diesel Exhaust Emissions
R834677C160 Personal and Ambient Exposures to Air Toxics in Camden, New Jersey
R834677C162 Assessing the Impact of a Wood Stove Replacement Program on Air Quality and Children’s Health
R834677C163 The London Low Emission Zone Baseline Study
R834677C165 Effects of Controlled Exposure to Diesel Exhaust in Allergic Asthmatic Individuals
R834677C168 Evaluating the Effects of Title IV of the 1990 Clean Air Act Amendments on Air Quality
R834677C172 Potential Air Toxics Hot Spots in Truck Terminals and Cabs
R834677C173 Detection and Characterization of Nanoparticles from Motor Vehicles
R834677C174 Cardiorespiratory Biomarker Responses in Healthy Young Adults to Drastic Air Quality Changes Surrounding the 2008 Beijing Olympics