Interleukin-34 induces Cc-chemokine ligand 20 in gut epithelial cells

Eleonora Franzè, Irene Marafini, Veronica De Simone, Ivan Monteleone, Flavio Caprioli, Alfredo Colantoni, Angela Ortenzi, Francesca Crescenzi, Roberta Izzo, Giuseppe Sica, Pier Paolo Sileri, Piero Rossi, Francesco Pallone, Giovanni Monteleone

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)87-94
Number of pages8
JournalJournal of Crohn's & colitis
Volume10
Issue number1
DOIs
Publication statusPublished - Jan 1 2016

Keywords

  • cytokines; chemokines; intestinal epithelium
  • Inflammatory bowel disease; colitis

ASJC Scopus subject areas

  • Gastroenterology

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