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* Department of Biology, Georgia State University, Atlanta, GA 30303; and
Biosciences Division, Argonne National Laboratory, Argonne, IL 60439
Receptor for advanced glycation endproducts (RAGE) is an Ig superfamily cell surface receptor that interacts with a diverse array of ligands associated with inflammatory responses. In this study, we provide evidence demonstrating that RAGE is involved in inflammatory responses in the intestines. We showed that RAGE is expressed in intestinal epithelial cells, primarily concentrated at the lateral membranes close to the apical cell junction complexes. Although RAGE expression was low in epithelium under normal conditions, this protein was up-regulated after treatment with the inflammatory cytokines IFN-
and/or TNF-
. RAGE expression was also elevated in colon tissue samples from patients with inflammatory bowel diseases. Using in vitro transmigration assays, we found that RAGE mediates neutrophil (polymorphonuclear leukocytes (PMN)) adhesion to, and subsequent migration across, intestinal epithelial monolayers. This activity appears to be mediated by the binding of RAGE to the PMN-specific 
2 integrin CD11b/CD18. Thus, these results provide a novel mechanism for the regulation of PMN transepithelial migration and may suggest a new therapeutic target for intestinal inflammation.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported, in part, by a scientist development grant (to K.Z.), a Beginning Grant-in-Aid (to Y.L.) from the American Heart Association, and a National Institutes of Health Grant DK62894 (to Y.L.).
2 Address correspondence and reprint requests to Yuan Liu, Cellular Molecular Biology and Physiology, Department of Biology, Georgia State University, Atlanta, GA 30303. E-mail address: bioyxl{at}langate.gsu.edu
3 Abbreviations used in this paper: PMN, polymorphonuclear leukocyte; IBD, inflammatory bowel disease; JAM, junction adhesion molecule; RAGE, receptor for advanced glycation endproduct; UC, ulcerative colitis; exRAGE, RAGE extracellular domain; GST, glutathione S-transferase; E-cad, E-cadherin; ZO-1, zona occludence protein-1; FBG, fibrinogen; BCECF, 2',7'-bis-(2-carboxyethyl)-(and-6)-carboxyfluo-rescein; DAF, decay-accelerating factor.
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