Interleukin-34 Induces Cc-chemokine Ligand 20 in Gut Epithelial Cells.

Abstract

BACKGROUND AND AIM:

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: Eleonora Franzè, Irene Marafini, Veronica De Simone, Ivan Monteleone, Flavio Caprioli, Alfredo Colantoni, Angela Ortenzi, Francesca Crescenzi, Roberta Izzo, Giuseppe Sica, PierPaolo Sileri, Piero Rossi, Francesco Pallone, Giovanni Monteleone
• Journal: Journal of Crohn's & colitis (J Crohns Colitis) Vol. 10 Issue 1 Pg. 87-94 (Jan 2016) ISSN: 1876-4479 [Electronic] England
• PMID: 26449789 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: [email protected].

Chemical References

• Biomarkers
• Chemokine CCL20
• IL34 protein, human
• Interleukins
• Receptor, Macrophage Colony-Stimulating Factor

Topics

• Biomarkers (metabolism)
• Biopsy, Needle
• Blotting, Western
• Cells, Cultured
• Chemokine CCL20 (metabolism)
• Colitis, Ulcerative (immunology, pathology)
• Colonoscopy (methods)
• Crohn Disease (immunology, pathology)
• Enzyme-Linked Immunosorbent Assay
• Epithelial Cells (immunology, metabolism)
• Female
• Humans
• Immunohistochemistry
• Interleukins (metabolism)
• Intestinal Mucosa (cytology, immunology, metabolism)
• Male
• Real-Time Polymerase Chain Reaction
• Receptor, Macrophage Colony-Stimulating Factor (metabolism)
• Sensitivity and Specificity
• Up-Regulation