title: Interleukin-34 Induces Cc-chemokine Ligand 20 in Gut Epithelial Cells.
abstract: OBJECTIVE
  Production of chemokines by intestinal epithelial cells is a key step in the amplification of the destructive immune-inflammatory response in patients with inflammatory bowel diseases [IBD]. In this study, we examined whether intestinal epithelial cells express macrophage colony-stimulating factor receptor 1 [M-CSFR-1], the functional receptor of interleukin-34 [IL-34], a cytokine that is over-produced in IBD and supposed to sustain inflammatory pathways.
  
  
  METHODS
  M-CSFR-1 expression was evaluated in intestinal samples of IBD patients, controls, and colon epithelial cell lines by real-time polymerase chain reaction [PCR], immunohistochemistry, and western blotting. DLD-1 cells were stimulated with IL-34 in the presence or absence of MAP kinase inhibitors, chemokine induction was assessed by real-time PCR and enzyme-linked immunosorbent assay [ELISA], and mitogen-activated protein (MAP) kinase activation was monitored by western blotting. The effect of a neutralising IL-34 antibody on CC chemokine ligand (CCL) 20 synthesis was tested in ex vivo organ cultures of IBD mucosal explants.
  
  
  RESULTS
  Enhanced expression of M-CSFR-1 RNA transcripts was seen in inflamed mucosa of IBD patients as compared with controls. Immunohistochemical analysis confirmed up-regulation of M-CSFR-1 in IBD and showed that both epithelial and lamina propria mononuclear cells expressed this receptor. Stimulation of DLD-1 with IL-34 increased CCL20 production through an ERK1/2-dependent mechanism. Consistently, treatment of IBD explants with anti-IL-34 reduced CCL20 production.
  
  
  CONCLUSIONS
  These data show that intestinal epithelial cells are a target of IL-34 and suggest that this cytokine contributes to mediating the cross-talk between epithelial cells and immune cells in IBD.
authors.affiliation: Department of Systems Medicine, University of Rome 'TOR VERGATA', Rome, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Franzè
authors.affiliation: Department of Systems Medicine, University of Rome 'TOR VERGATA', Rome, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Marafini
authors.affiliation: Department of Systems Medicine, University of Rome 'TOR VERGATA', Rome, Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: De Simone
authors.affiliation: Department of Systems Medicine, University of Rome 'TOR VERGATA', Rome, Italy.
authors.forename: Ivan
authors.initials: I
authors.lastname: Monteleone
authors.affiliation: Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.
authors.forename: Flavio
authors.initials: F
authors.lastname: Caprioli
authors.affiliation: Department of Systems Medicine, University of Rome 'TOR VERGATA', Rome, Italy.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Colantoni
authors.affiliation: Department of Systems Medicine, University of Rome 'TOR VERGATA', Rome, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Ortenzi
authors.affiliation: Department of Systems Medicine, University of Rome 'TOR VERGATA', Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Crescenzi
authors.affiliation: Department of Systems Medicine, University of Rome 'TOR VERGATA', Rome, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Izzo
authors.affiliation: Department of Surgery, University of Rome 'TOR VERGATA', Rome, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Sica
authors.affiliation: Department of Surgery, University of Rome 'TOR VERGATA', Rome, Italy.
authors.forename: PierPaolo
authors.initials: P
authors.lastname: Sileri
authors.affiliation: Department of Surgery, University of Rome 'TOR VERGATA', Rome, Italy.
authors.forename: Piero
authors.initials: P
authors.lastname: Rossi
authors.affiliation: Department of Systems Medicine, University of Rome 'TOR VERGATA', Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Pallone
authors.affiliation: Department of Systems Medicine, University of Rome 'TOR VERGATA', Rome, Italy Gi.Monteleone@Med.uniroma2.it.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Monteleone
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D001707:Biopsy, Needle; D015153:Blotting, Western; D002478:Cells, Cultured; D054418:Chemokine CCL20 / Q000378:metabolism*; D003093:Colitis, Ulcerative / Q000276:immunology / Q000473:pathology; D003113:Colonoscopy / Q000379:methods; D003424:Crohn Disease / Q000276:immunology / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007378:Interleukins / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D008297:Male; D060888:Real-Time Polymerase Chain Reaction; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D012680:Sensitivity and Specificity; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D054418:Chemokine CCL20; C529076:IL34 protein, human; D007378:Interleukins; D016186:Receptor, Macrophage Colony-Stimulating Factor
keywords: Inflammatory bowel disease; colitis; cytokines; chemokines; intestinal epithelium