Ultrafine Particle Cell Interactions In Vitro: Molecular Mechanisms Leading To Altered Gene Expression in Relation to Particle Composition

EPA Grant Number: R832415C005
Subproject: this is subproject number 005 , established and managed by the Center Director under grant R832415
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).

Center: Rochester PM Center
Center Director: Oberd√∂rster, G√ľnter
Title: Ultrafine Particle Cell Interactions In Vitro: Molecular Mechanisms Leading To Altered Gene Expression in Relation to Particle Composition
Investigators: Finkelstein, Jacob N. , Oakes, David , Phipps, Richard , Prather, Kimberly A. , Rahman, Arshad
Institution: University of Rochester , University of California - San Diego
EPA Project Officer: Hunt, Sherri
Project Period: October 1, 2005 through September 30, 2010 (Extended to September 30, 2012)
RFA: Particulate Matter Research Centers (2004) RFA Text |  Recipients Lists
Research Category: Health Effects , Air

Objective:

These studies are designed to address specific mechanistic hypotheses regarding the interactions between inhaled ultrafine particles and specific pulmonary and cardiovascular cell populations. We will use cell lines and primary cells derived from rats and humans to test the hypothesis that increased morbidity and mortality in susceptible populations is due to the unique characteristics of ultrafine particles inducing oxidative stress and activation of target cells. It is further suggested that this ability is based on composition that is related to specific sources.

Approach:

Studies will use isolated and cultured cells that have been identified as the principle targets of inhaled PM and carry out hypothesis testing studies that support the in vivo studies (Cores 3 and 4). Cell specific endpoints of PM induced toxicity for inflammatory, epithelial and vascular endothelial cells will be determined in a dose-responsive manner. These cells will be obtained from both human and animal tissues. Our use of multiple endpoints ensures that we can determine the relationship between a cellular response and the critical variable of a specific particle. We plan studies with both "real world" and laboratory generated PM of known composition that may represent specific sources to establish source related effects.

Expected Results:

The results of these in vitro studies will identify specific mechanisms that are triggered following particle cell contact in a cell specific context and identify markers of cellular response. We predict that many of the subsequent physiologic effects in vivo are the consequences of cellular oxidative stress, cell activation and apoptosis. The proposed in vitro experiments will provide a link between the whole animal and controlled clinical (human) exposures, described in the other programs of this PM Center, By evaluating "source specific" responses in vitro we can determine the relative potency of a given particle type and allow for studies in vivo to be more focused and mechanism based. These studies may also provide information regarding strategies to reduce PM effects. As correlations are established between in vitro responses and whole organism studies, the in vitro studies, which require less material and a shorter time frame, may be applied as a routine screen for potential PM risk and as support for setting regulatory standards.

Publications and Presentations:

Publications have been submitted on this subproject: View all 13 publications for this subprojectView all 169 publications for this center

Journal Articles:

Journal Articles have been submitted on this subproject: View all 10 journal articles for this subprojectView all 122 journal articles for this center

Supplemental Keywords:

Cytokines, antioxidants, diabetes,, RFA, Health, Scientific Discipline, PHYSICAL ASPECTS, Air, particulate matter, Genetics, Health Risk Assessment, Risk Assessments, Physical Processes, Biology, altered gene expression, atmospheric particulate matter, atmospheric particles, long term exposure, airway disease, exposure, human exposure, ambient particle health effects, atmospheric aerosol particles, PM, aersol particles

Progress and Final Reports:

2006 Progress Report
2007 Progress Report
2008 Progress Report
2009 Progress Report
2010 Progress Report
2011 Progress Report
Final Report


Main Center Abstract and Reports:

R832415    Rochester PM Center

Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R832415C001 Characterization and Source Apportionment
R832415C002 Epidemiological Studies on Extra Pulmonary Effects of Fresh and Aged Urban Aerosols from Different Sources
R832415C003 Human Clinical Studies of Concentrated Ambient Ultrafine and Fine Particles
R832415C004 Animal models: Cardiovascular Disease, CNS Injury and Ultrafine Particle Biokinetics
R832415C005 Ultrafine Particle Cell Interactions In Vitro: Molecular Mechanisms Leading To Altered Gene Expression in Relation to Particle Composition