Associate Provost for Research Boston University Medical Campus
NIDDK - National Institute of Diabetes & Digestive & Kidney Diseases	Research Resources

Abstract

Abstract: DESCRIPTION (provided by applicant): 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.

Thesaurus Terms:
chemokine, gastrointestinal epithelium, inflammation, inflammatory bowel disease, peroxisome proliferator activated receptor, rosiglitazone, thiazole
IP 10 protein, biological signal transduction, enzyme activity, interferon gamma, ligand, mitogen activated protein kinase, phosphorylation
SDS polyacrylamide gel electrophoresis, enzyme linked immunosorbent assay, immunoprecipitation, polymerase chain reaction, postdoctoral investigator, western blotting

Institution:	BOSTON MEDICAL CENTER
	ONE BOSTON MEDICAL CENTER PLACE
	BOSTON, MA 02118
Fiscal Year:	2006
Department:
Project Start:	01-MAR-2004
Project End:	31-MAR-2006
ICD:	NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
IRG:	ZRG1