Ozone is a ubiquitous urban air pollutant known to cause alveolar epithelial injury. A characteristic pulmonary reaction to inhaled ozone is an increase in the number of activated alveolar macrophages and type II epithelial cells in the lung. A variety of mediators produced by these cells, in particular the reactive nitrogen intermediates nitric oxide and peroxynitrite, can contribute to tissue injury. Nitric oxide is generated in the cells via the inducible form of nitric oxide synthase (NOS2). One protein that has been identified as a key endogenous mediator of ozone-induced toxicity is heat shock protein 60 (HSP 60). The overall objectives of the proposed studies are to analyze the role of HSP 60 in the production of NOS2 by alveolar macrophages and type II cells in ozone-induced toxicity. Our hypothesis is that HSP 60 contributes to ozone toxicity, not just by inducing nitric oxide production, but also by stimulating the release of proinflammatory cytokines that can synergize with HSP 60 to generate excessive quantities of nitric oxide in the lung which contribute to tissue injury.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32ES011932-01
Application #
6552727
Study Section
Special Emphasis Panel (ZRG1-F10 (20))
Program Officer
Shreffler, Carol K
Project Start
2002-07-15
Project End
Budget Start
2002-07-15
Budget End
2003-07-14
Support Year
1
Fiscal Year
2002
Total Cost
$36,592
Indirect Cost
Name
Rutgers University
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
038633251
City
New Brunswick
State
NJ
Country
United States
Zip Code
08901