title: Expression and regulation of the chemokine CXCL16 in Crohn's disease and models of intestinal inflammation.
abstract: BACKGROUND
  CXCL16 mediates adhesion and phagocytosis of both Gram-negative and Gram-positive bacteria and is a strong chemoattractant for CXCR6+ T cells. In this study, we determined the so far unknown expression and signal transduction of the novel CXCL16-CXCR6 chemokine-ligand receptor system in intestinal inflammation in vivo and in vitro.
  
  
  METHODS
  CXCL16 mRNA was measured by quantitative PCR in human colonic biopsies of patients with Crohn's disease (CD) as well as in the TNFΔARE mouse model of ileitis and in murine cytomegalovirus (MCMV)-induced colitis. CXCL16 serum levels were analyzed by ELISA. CXCL16-induced signal transduction was analyzed in intestinal epithelial cells with phospho-specific antibodies for mitogen-activated protein (MAP) kinases and Akt.
  
  
  RESULTS
  We found an inverse expression pattern of CXCL16 and CXCR6, with highest CXCL16 mRNA expression in the proximal murine small intestine and the highest CXCR6 mRNA expression in the distal colon. CXCL16 and CXCR6 mRNA were expressed in colorectal cancer (CRC)-derived intestinal epithelial cell (IEC) lines. CRC-expressed CXCR6 was functional, as demonstrated by CXCL16-induced MAP kinase and Akt activation. Intestinal CXCL16 expression was elevated in the TNFΔARE mouse model of ileitis and in MCMV-induced colitis (P < 0.05) and in the sera and colons of patients with CD (P < 0.05), where its expression correlated highly with CXCR6 and IL-8 levels (r = 0.85 and 0.89, respectively).
  
  
  CONCLUSIONS
  CRC-derived IECs express the functional CXCL16 receptor CXCR6. CXCL16 mRNA and protein expression is up-regulated in intestinal inflammation in vitro and in CD patients, suggesting an important role for this chemokine in intestinal inflammation.
authors.affiliation: Department of Internal Medicine II-Grosshadern, University of Munich, Munich, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Diegelmann
authors.forename: Julia
authors.initials: J
authors.lastname: Seiderer
authors.forename: Jan-Hendrik
authors.initials: JH
authors.lastname: Niess
authors.forename: Dirk
authors.initials: D
authors.lastname: Haller
authors.forename: Burkhard
authors.initials: B
authors.lastname: Göke
authors.forename: Hans-Christian
authors.initials: HC
authors.lastname: Reinecker
authors.forename: Stephan
authors.initials: S
authors.lastname: Brand
mesh_terms: D000818:Animals; D002460:Cell Line; D000075743:Chemokine CXCL16; D054427:Chemokine CXCL6 / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D019743:Chemokines, CXC / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D003092:Colitis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D003106:Colon / Q000276:immunology / Q000378:metabolism; D003424:Crohn Disease / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D006566:Herpesviridae Infections / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007079:Ileitis / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000032:analysis / Q000378:metabolism; D018146:Muromegalovirus / Q000276:immunology / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000276:immunology / Q000378:metabolism; D054387:Receptors, CXCR / Q000276:immunology / Q000378:metabolism; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine / Q000276:immunology / Q000378:metabolism; D051116:Receptors, Scavenger / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D011991:Receptors, Virus / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C423727:CXCL16 protein, human; C106330:CXCR6 protein, human; D000075743:Chemokine CXCL16; D054427:Chemokine CXCL6; D019743:Chemokines, CXC; C498926:Cxcl16 protein, mouse; C482906:Cxcr6 protein, mouse; D054387:Receptors, CXCR; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine; D051116:Receptors, Scavenger; D011991:Receptors, Virus; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases