The objective of this study is to understand the roles that peroxisome proliferator-activated receptors (PPARs) have in the lung. We have shown that PPARb and PPARg are highly expressed in lung alveolar type II and Type I cells. We are using an in vitro cell system of murine Type II cells, specific PPAR ligands, and PPARa and PPARb knockout mice to study the function of these nuclear receptors in normal lung and during lung inflammatory disease including fibrosis and asthma. Cells were treated with PPAR-specific ligands, RNA isolated and used in microarray analysis in order to identify genes genes regulated by PPAR. These studies have identified several genes that regulated by PPARs in a time and dose-dependent manner. In addition, we are examining the interaction between cytokine and PPAR signaling. We have shown that treatment of human lung fibroblasts with interleukin 1b downregulates PPARg expression. This down-regulation is specific for IL-1b and TNF-a and is not observed with other interleukins including IL-3, IL-13, Il-8, and IL4. The decrease in PPARg expression is prevented by dexamethasone. These results suggest crosstalk between different receptor and cytokine pathways.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Intramural Research (Z01)
Project #
1Z01ES100484-01
Application #
6673284
Study Section
(LPP)
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2002
Total Cost
Indirect Cost
Name
U.S. National Inst of Environ Hlth Scis
Department
Type
DUNS #
City
State
Country
United States
Zip Code