Functions of PPAR in the lung

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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.