Science Inventory

TRANSCRIPTION FACTOR ACTIVATION FOLLOWING EXPOSURE OF AN INTACT LUNG PREPARATION TO METALLIC PARTICULATE MATTER

Citation:

Samet, J M., R Silbajoris, Huang, YuhChin T, AND I. Jaspers. TRANSCRIPTION FACTOR ACTIVATION FOLLOWING EXPOSURE OF AN INTACT LUNG PREPARATION TO METALLIC PARTICULATE MATTER. ENVIRONMENTAL HEALTH PERSPECTIVES. National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, NC, 110(10):985-990, (2002).

Description:

TRANSCRIPTION FACTOR ACTIVATION FOLLOWING EXPOSURE OF AN INTACT LUNG PREPARATION TO METALLIC PARTICULATE MATTER

James M. Samet1,2, Robert Silbajoris1, Tony Huang1 and Ilona Jaspers3

1Human Studies Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, and 3Center for Environmental Medicine and Lung Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
2 The authors of this manuscript contributed equally to it. Correspondence may be addressed to any of them at the following address:

104 Mason Farm Rd.
EPA Human Studies Facility
Chapel Hill, NC 27599
Tel.: 919 966-0665
FAX: 919 966-6271
E-mail: samet.jim@epa.govABSTRACT
Metallic constituents contained in ambient PM have been associated with adverse effects in a number of epidemiologic, in vitro and in vivo studies. Residual oil fly ash (ROFA) is a metallic by-product of the combustion of fossil fuel oil which has been shown to induce a variety of pro-inflammatory responses in lung cells. We have examined signaling pathways activated in response to ROFA exposure and recently reported that ROFA treatment activates multiple MAP kinases in the rat lung. In the present study we have extended our investigations on the mechanism of toxicity of ROFA to include transcription factors whose activities are regulated by MAP kinases as well as possible effectors of transcriptional changes that mediate the effects of ROFA. We have applied immunohistochemical methods to detect ROFA-induced activation of NFkB, ATF-2, c-Jun and CREB in intact lung tissue and confirmed and characterized their functional activation using DNA binding assays. We have performed these studies using a perfused rabbit lung model that is devoid of blood elements in order to distinguish between intrinsic lung cell effects and effects that are secondary to inflammatory cell influx. We report here that exposure to ROFA results in a rapid activation of all of the transcription factors studied by exerting direct effects on lung cells. These findings validate the use of immunohistochemistry to detect transcription factor activation in vivo and demonstrate the utility of studying signaling changes in response to environmental exposures.

Record Details:

Record Type: DOCUMENT (JOURNAL/PEER REVIEWED JOURNAL)
Product Published Date: 10/01/2002
Record Last Revised: 12/22/2005
Record ID: 65736

Organization:

U.S. ENVIRONMENTAL PROTECTION AGENCY

OFFICE OF RESEARCH AND DEVELOPMENT

NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY

HUMAN STUDIES DIVISION

CLINICAL RESEARCH BRANCH