Interleukin-34 sustains inflammatory pathways in the gut

Eleonora Franzé, Ivan Monteleone, Maria Laura Cupi, Pamela Mancia, Flavio Caprioli, Irene Marafini, Alfredo Colantoni, Angela Ortenzi, Federica Laudisi, Giuseppe Sica, PierPaolo Sileri, Francesco Pallone, Giovanni Monteleone

Research output: Contribution to journalArticlepeer-review

Abstract

IBD (inflammatory bowel disease)-related tissue damage occurs in areas which are massively infiltrated with monocytes/macrophages. These cells respond to inflammatory stimuli with enhanced production of cytokines/chemokines. In the present study, we analysed the expression and role of IL (interleukin)-34, a regulator of monocyte/macrophage differentiation, survival and function, in IBD. A significant increase in IL-34 mRNA and protein expression was seen in inflamed mucosa of patients with CD (Crohn's disease) and patients with UC (ulcerative colitis) compared with the uninvolved areas of the same patients and normal controls. IL-34 was up-regulated in LPMCs (lamina propria mononuclear cells) isolated from normal colon by TNF-α (tumour necrosis factor α) and TLR (Toll-like receptor) ligands and was down-regulated in intestinal biopsies and LPMCs of IBD patients upon treatment with infliximab. Treatment of normal LPMCs with IL-34 increased TNF-α expression in an ERK1/2 (extracellular-signal-regulated kinase 1/2)-dependent fashion and neutralization of IL-34 in IBD mucosal explants reduced TNF-α and IL-6 synthesis. In conclusion, our results indicate that IL-34 is up-regulated in IBD and suggest a role for this cytokine in sustaining the inflammatory responses in this disease.

Original languageEnglish
Pages (from-to)271-280
Number of pages10
JournalClinical Science
Volume129
Issue number3
DOIs
Publication statusPublished - 2015

Keywords

  • Crohn's disease
  • Cytokines
  • Immunity
  • Intestine
  • Mucosal inflammation
  • Ulcerative colitis

ASJC Scopus subject areas

  • Medicine(all)

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