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Ultrafine Particle Cell Interactions: Molecular Mechanisms Leading to Altered Gene Expression
EPA Grant Number: R827354C005Subproject: this is subproject number 005 , established and managed by the Center Director under grant R827354
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: Airborne PM - Rochester PM Center
Center Director: Oberdorster, Gunter
Title: Ultrafine Particle Cell Interactions: Molecular Mechanisms Leading to Altered Gene Expression
Investigators: Finkelstein, Jacob N. , Gelein, Robert , O'Reilly, Michael , Oberdörster, Günter , Phipps, Richard
Current Investigators: Finkelstein, Jacob N.
Institution: University of Rochester
EPA Project Officer: Stacey Katz/Gail Robarge,
Project Period: June 1, 1999 through May 31, 2005 (Extended to May 31, 2006)
RFA: Airborne Particulate Matter (PM) Centers (1999)
Research Category: Particulate Matter
Description:
Objective:The objective of this research project is to develop in vitro models useful for understanding the mechanism of ultrafine particle induced gene expression in various cell types. The objective is for these models to define mechanisms of cellular activation, the effects of age or prior activation on cytokine gene activation, and differential responses of epithelial cells and macrophages to particles of different sizes.
Approach:This year we will characterize the differences in response to stimuli, alone and in combination, on the effect of age. Mouse macrophages show an age dependent difference in cytokine production following stimulation with particles or lipopolysaccharide (LPS). We will compare macrophage production of cytokines following LPS and particle incubation with cells from 8-10 week old mice and 20-22 month old mice. When macrophages from young mice are treated with LPS, a clear dose response, with macrophage inflammatory protein-2 (MIP-2) as the endpoint, will be obtained and analyzed. We also will continue to use the cell lines we developed for more detailed mechanistic studies of our oxidant stress hypothesis.
Expected Results:We expect the in vitro models to differentiate between particles of differing toxicity and activation potential, these models also may prove useful in studies of other size fractions.
Publications and Presentations:Publications have been submitted on this subproject: View all 9 publications for this subproject | View all 87 publications for this center
Journal Articles:Journal Articles have been submitted on this subproject: View all 7 journal articles for this subproject | View all 78 journal articles for this center
Supplemental Keywords:ultrafine, particle, lipopolysaccharide, LPS, gene, animal model, human model. , Air, Scientific Discipline, Health, RFA, Molecular Biology/Genetics, Toxicology, Risk Assessments, Health Risk Assessment, air toxics, Atmospheric Sciences, Biochemistry, particulate matter, Environmental Chemistry, aerosols, cardiopulmonary, risk assessment, susceptible populations, ultrafine particles, altered gene expression, urban environment, aerosol, ambient air quality, cardiovascular disease, cardiovascular vulnerability, coronary artery disease, health effects, mortality, lung inflamation, inhalation toxicology, ambient air, fine particles, environmental health effects, cardiopulmonary responses, human health risk, cytokine production, particle exposure, biostatistics, human health effects, particulates, sensitive populations, ambient monitoring, lung, metals, ambient air monitoring, pathophysiological mechanisms, atmospheric, pulmonary, urban air pollution, human health, cell kinetic models, morbidity, particle size, PM, pulmonary disease, animal model
Progress and Final Reports:
1999 Progress Report
2000 Progress Report
2001 Progress Report
2002 Progress Report
2003 Progress Report
2004 Progress Report
Final Report
Main Center Abstract and Reports:
R827354 Airborne PM - Rochester PM Center
Subprojects under this Center:
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R827354C001 Characterization of the Chemical Composition of Atmospheric Ultrafine Particles
R827354C002 Inflammatory Responses and Cardiovascular Risk Factors in Susceptible Populations
R827354C003 Clinical Studies of Ultrafine Particle Exposure in Susceptible Human Subjects
R827354C004 Animal Models: Dosimetry, and Pulmonary and Cardiovascular Events
R827354C005 Ultrafine Particle Cell Interactions: Molecular Mechanisms Leading to Altered Gene Expression
R827354C006 Development of an Electrodynamic Quadrupole Aerosol Concentrator
R827354C007 Kinetics of Clearance and Relocation of Insoluble Ultrafine Iridium Particles From the Rat Lung Epithelium to Extrapulmonary Organs and Tissues (Pilot Project)
R827354C008 Ultrafine Oil Aerosol Generation for Inhalation Studies