Receptor for advanced glycation endproducts mediates neutrophil migration across intestinal epithelium.
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-gamma and/or TNF-alpha. 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 beta(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.
Zen
Ke
K
Department of Biology, Georgia State University, Atlanta, GA 30303, USA.
Chen
Celia X-J
CX
Chen
Yi-Tien
YT
Wilton
Rosemarie
R
Liu
Yuan
Y
D039481:CD11b Antigen / Q000276:immunology; D018821:CD18 Antigens / Q000276:immunology; D002465:Cell Movement / Q000276:immunology*; D003106:Colon / Q000276:immunology / Q000473:pathology; D004847:Epithelial Cells / Q000276:immunology* / Q000473:pathology; D004848:Epithelium / Q000276:immunology / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D007365:Intercellular Junctions / Q000276:immunology / Q000473:pathology; D007371:Interferon-gamma / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology / Q000473:pathology; D009504:Neutrophils / Q000276:immunology* / Q000473:pathology; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D039481:CD11b Antigen; D018821:CD18 Antigens; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma