title: Fractalkine-mediated signals regulate cell-survival and immune-modulatory responses in intestinal epithelial cells.
abstract: OBJECTIVE
  In this study, we determined the signal transduction and functional consequences after ligand-specific activation of the fractalkine receptor CX3CR1 in human intestinal epithelial cells.
  
  
  METHODS
  CX3CR1 expression in human colonic tissues and intestinal epithelial cell lines was determined by immunohistochemistry, immunoblotting, and reverse-transcription polymerase chain reaction. The regulation of mitogen-activated protein kinase (MAPK) activation was assessed by immunoblotting. Regulation of chemokine messenger RNA (mRNA) expression was determined by Northern blotting. NF-kappa B and p53 activation was assessed by electromobility shift assays.
  
  
  RESULTS
  Fractalkine mediated the MEK-1 and G alpha i-dependent but phosphatidylinositol-3-kinase-independent activation of extracellular signal-regulated kinase-MAPK. Fractalkine activated NF-kappa B and p53 resulting in interleukin 8 and fractalkine mRNA expression. CX3CR1-mediated activation of intestinal epithelial cells was able to induce migration of human neutrophils into but not through the intestinal epithelial cell monolayer.
  
  
  CONCLUSIONS
  CX3CR1 mediates distinct functional responses in intestinal epithelial cells, which include the autocrine regulation of cell-survival signals and activation of immune modulators, indicating a role of CX3CR1 in host defense mechanisms originating from the intestinal epithelium.
authors.affiliation: Gastrointestinal Unit, Department of Medicine, Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.
authors.forename: Stephan
authors.initials: S
authors.lastname: Brand
authors.forename: Takanori
authors.initials: T
authors.lastname: Sakaguchi
authors.forename: Xiubin
authors.initials: X
authors.lastname: Gu
authors.forename: Sean P
authors.initials: SP
authors.lastname: Colgan
authors.forename: Hans-Christian
authors.initials: HC
authors.lastname: Reinecker
mesh_terms: D000276:Adjuvants, Immunologic / Q000378:metabolism*; D019898:Autocrine Communication / Q000276:immunology; D000073883:CX3C Chemokine Receptor 1; D018938:Caco-2 Cells; D002455:Cell Division / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival / Q000502:physiology; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D048369:MAP Kinase Kinase 1; D020935:MAP Kinase Signaling System / Q000276:immunology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D018121:Receptors, Cytokine / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D015728:Receptors, HIV / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D013274:Stomach Neoplasms; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; D000073883:CX3C Chemokine Receptor 1; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D048369:MAP Kinase Kinase 1; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020929:Mitogen-Activated Protein Kinase Kinases; D020928:Mitogen-Activated Protein Kinases; D016328:NF-kappa B; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D018121:Receptors, Cytokine; D015728:Receptors, HIV; D016159:Tumor Suppressor Protein p53; C482125:MAP2K1 protein, human