title: Colonic epithelial cells are a major site of macrophage inflammatory protein 3alpha (MIP-3alpha) production in normal colon and inflammatory bowel disease.
abstract: OBJECTIVE
  Macrophage inflammatory protein 3alpha (MIP-3alpha) is a recently described lymphocyte directed C-C chemokine expressed predominately at extralymphoid sites, including the intestine. The aim of this study was to determine whether colonic epithelial cells produce MIP-3alpha and whether its expression is upregulated in inflammatory bowel disease.
  
  
  RESULTS
  We found that interleukin 1beta and tumour necrosis factor alpha dose dependently stimulated MIP-3alpha production in Caco-2 and HT-29 intestinal epithelial cells. In cytokine treated Caco-2 and HT-29 cells, a significant increase in MIP-3alpha protein production was observed after three hours and continued for at least 24 hours. Analysis of colonic tissues by quantitative real time polymerase chain reaction and ELISA revealed significantly elevated MIP-3alpha mRNA levels (7.9-fold; p<0.05) and protein levels (8.9-fold; p<0.05) in Crohn's disease compared with controls or ulcerative colitis. MIP-3alpha immunoreactivity in normal colon and inflammatory bowel disease was principally associated with crypt and surface epithelial cells. Moreover, MIP-3alpha protein levels were elevated in primary epithelial cells isolated from patients with inflammatory bowel disease.
  
  
  CONCLUSIONS
  These findings indicate that increased enterocyte MIP-3alpha production may play an important role in lymphocyte activation and recruitment to the colonic epithelium in Crohn's disease and ulcerative colitis.
authors.affiliation: Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston MA 02215, USA.
authors.forename: J H
authors.initials: JH
authors.lastname: Kwon
authors.forename: S
authors.initials: S
authors.lastname: Keates
authors.forename: L
authors.initials: L
authors.lastname: Bassani
authors.forename: L F
authors.initials: LF
authors.lastname: Mayer
authors.forename: A C
authors.initials: AC
authors.lastname: Keates
mesh_terms: D015415:Biomarkers / Q000032:analysis; D018938:Caco-2 Cells; D054418:Chemokine CCL20; D019742:Chemokines, CC / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D003093:Colitis, Ulcerative / Q000276:immunology; D003424:Crohn Disease / Q000276:immunology; D005786:Gene Expression Regulation; D019073:HT29 Cells; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000276:immunology*; D007376:Interleukin-2 / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000276:immunology*; D019402:Macrophage Inflammatory Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000032:analysis; D054399:Receptors, CCR6; D019707:Receptors, Chemokine; D013268:Stimulation, Chemical; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D015415:Biomarkers; C108355:CCL20 protein, human; C106311:CCR6 protein, human; D054418:Chemokine CCL20; D019742:Chemokines, CC; D007376:Interleukin-2; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger; D054399:Receptors, CCR6; D019707:Receptors, Chemokine; D014409:Tumor Necrosis Factor-alpha