Ultrafine Particle Cell Interactions: Molecular Mechanisms Leading to Altered Gene Expression

EPA Grant Number: R827354C005
Subproject: 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: Rochester PM Center
Center Director: Oberdörster, Günter
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: Chung, Serena
Project Period: June 1, 1999 through May 31, 2005 (Extended to May 31, 2006)
RFA: Airborne Particulate Matter (PM) Centers (1999) RFA Text |  Recipients Lists
Research Category: Air Quality and Air Toxics , Particulate Matter , Air

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 subprojectView all 104 publications for this center

Journal Articles:

Journal Articles have been submitted on this subproject: View all 7 journal articles for this subprojectView all 90 journal articles for this center

Supplemental Keywords:

ultrafine, particle, lipopolysaccharide, LPS, gene, animal model, human model., RFA, Health, Scientific Discipline, Air, particulate matter, Toxicology, air toxics, Environmental Chemistry, Health Risk Assessment, Risk Assessments, Biochemistry, Atmospheric Sciences, Molecular Biology/Genetics, ambient air quality, cytokine production, particle size, particulates, sensitive populations, biostatistics, atmospheric, health effects, risk assessment, altered gene expression, cardiopulmonary responses, fine particles, human health effects, morbidity, ambient air monitoring, lung, cardiovascular vulnerability, pulmonary disease, susceptible populations, animal model, ambient air, environmental health effects, particle exposure, ambient monitoring, particulate exposure, lung inflamation, pulmonary, coronary artery disease, inhalation toxicology, urban air pollution, PM, mortality, urban environment, aerosol, cardiopulmonary, human health, aerosols, cardiovascular disease, ultrafine particles, pathophysiological mechanisms, metals, cell kinetic models

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    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