Inflammatory bowel diseases (IBD) are characterized by episodes of intestinal inflammation. Recent evidence suggests that activation of a nuclear receptor, PPAR-gamma, with a synthetic TZD ligand, BRL, offers protection against inflammation, at least in part by regulating inflammatory chemokine production from intestinal epithelial cells, both at the transcriptional and post-transcriptional levels. Interestingly, the chemokine promoters do not have PPAR-gamma response elements, indicating that the activated PPAR-gamma, or possibly BRL itself, affect chemokine production in """"""""non-classical"""""""" ways. In addition, BRL affects numerous rapid phosphorylation events after cellular stimulation, including many molecules involved in MAP kinase signaling. To test the hypothesis that activated PPAR-gamma or BRL itself regulate chemokine production by modulating MAP kinase signaling, the mechanisms of regulation of a representative chemokine, IP-10, will be determined. The effects of BRL on IP-10 regulation in the presence and absence of PPAR-gamma will be determined, and the signaling pathways affected by BRL delineated in detail. The results of these experiments will further understanding of the mechanism of action of synthetic PPAR-gamma ligands and help in the development of IBD therapies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32DK066928-01
Application #
6737753
Study Section
Special Emphasis Panel (ZRG1-F10 (20))
Program Officer
Podskalny, Judith M,
Project Start
2004-03-01
Project End
2007-02-28
Budget Start
2004-03-01
Budget End
2005-02-28
Support Year
1
Fiscal Year
2004
Total Cost
$56,536
Indirect Cost
Name
Boston Medical Center
Department
Type
DUNS #
005492160
City
Boston
State
MA
Country
United States
Zip Code
02118