The focus of the proposed research is the role of vitamin A (retinoids) in the prevention and modulation of environmental lung injury. The determinants of host susceptibility to environmental exposures and the interventions that could ameliorate such lung injury remain poorly understood. There is considerable evidence that vitamin A plays a role in these processes. The specific hypotheses of this proposal are: 1) Complex cytokine-cytokine networks play an important role in mediating radiation-induced lung injury. 2) Vitamin A is an important and potentially modifiable determinant of host susceptibility to lung inflammation and fibrosis and that local lung vitamin A levels may be a key determinant of such lung injury. 3) Retinoids may mediate their effects via their ability to regulate cytokine production and/or effector function. These hypotheses will be tested in a radiation-induced lung injury model.
The specific aims are to: 1) Characterize the cytokine- cytokine networks which regulate a) granulocyte recruitment, b) mast cell accumulation, and c) fibrosis at varying times following chest irradiation; 2) Characterize the role of lung vitamin A storage and metabolism in this model and the extent to which vitamin A prevents or ameliorates radiation-induced lung injury; 3) investigate the possible mechanisms by which vitamin A exerts its effects by determining whether altered vitamin A status modulates the lung cytokine networks involved. The proposed studies should add greatly to our understanding of the role of vitamin A in modulating inflammatory and fibrotic processes in the lung and the cytokine networks involved. At the same time these studies should also serve the major aim of the award, i.e. the production of an experienced, productive, independent researcher in environmental lung disease.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08HL003129-04
Application #
2635024
Study Section
Special Emphasis Panel (ZHL1-CCT-L (O1))
Project Start
1995-01-01
Project End
1999-12-31
Budget Start
1998-01-01
Budget End
1998-12-31
Support Year
4
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Yale University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520
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