HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 292/2/G657    most recent 00381.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (19) Citing Articles via Google Scholar Google Scholar Articles by Shah, Y. M. Articles by Gonzalez, F. J. Search for Related Content PubMed PubMed Citation Articles by Shah, Y. M. Articles by Gonzalez, F. J.

INFLAMMATION/IMMUNITY/MEDIATORS

Expression of peroxisome proliferator-activated receptor- in macrophage suppresses experimentally induced colitis

Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland

Submitted 16 August 2006 ; accepted in final form 2 November 2006

Peroxisome proliferator-activated receptor- (PPAR-) has been shown to be a protective transcription factor in mouse models of inflammatory bowel disease (IBD). PPAR- is expressed in several different cell types, and mice with a targeted disruption of the PPAR- gene in intestinal epithelial cells demonstrated increased susceptibility to dextran sulfate sodium (DSS)-induced IBD. However, the highly selective PPAR- ligand rosiglitazone decreased the severity of DSS-induced colitis and suppressed cytokine production in both PPAR- intestinal specific null mice and wild-type littermates. Therefore the role of PPAR- in different tissues and their contribution to the pathogenesis of IBD still remain unclear. Mice with a targeted disruption of PPAR- in macrophages (PPAR-^M) and wild-type littermates (PPAR-^F/F) were administered 2.5% DSS in drinking water to induce IBD. Typical clinical symptoms were evaluated on a daily basis, and proinflammatory cytokine analysis was performed. PPAR-^M mice displayed an increased susceptibility to DSS-induced colitis compared with wild-type littermates, as defined by body weight loss, diarrhea, rectal bleeding score, colon length, and histology. IL-1, CCR2, MCP-1, and inducible nitric oxide synthase mRNA levels in colons of PPAR-^M mice treated with DSS were higher than in similarly treated PPAR-^F/F mice. The present study has identified a novel protective role for macrophage PPAR- in the DSS-induced IBD model. The data suggest that PPAR- regulates recruitment of macrophages to inflammatory foci in the colon.

CC chemokine receptor 2; macrophages

This article has been cited by other articles:

				O. De Backer, E. Elinck, E. Priem, L. Leybaert, and R. A. Lefebvre Peroxisome Proliferator-Activated Receptor {gamma} Activation Alleviates Postoperative Ileus in Mice by Inhibition of Egr-1 Expression and Its Downstream Target Genes J. Pharmacol. Exp. Ther., November 1, 2009; 331(2): 496 - 503. [Abstract] [Full Text] [PDF]

				B. M. Necela, W. Su, and E. A. Thompson Peroxisome Proliferator-activated Receptor {gamma} Down-regulates Follistatin in Intestinal Epithelial Cells through SP1 J. Biol. Chem., October 31, 2008; 283(44): 29784 - 29794. [Abstract] [Full Text] [PDF]

				E. Thorp, G. Kuriakose, Y. M. Shah, F. J. Gonzalez, and I. Tabas Pioglitazone Increases Macrophage Apoptosis and Plaque Necrosis in Advanced Atherosclerotic Lesions of Nondiabetic Low-Density Lipoprotein Receptor Null Mice Circulation, November 6, 2007; 116(19): 2182 - 2190. [Abstract] [Full Text] [PDF]