title: Interleukin-34 sustains inflammatory pathways in the gut.
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.
authors: *Department of Systems Medicine, University of Rome "Tor Vergata", Via Montpellier 1, 00133 Rome, Italy.
authors: Eleonora
authors: E
authors: Franzè
authors: *Department of Systems Medicine, University of Rome "Tor Vergata", Via Montpellier 1, 00133 Rome, Italy.
authors: Ivan
authors: I
authors: Monteleone
authors: *Department of Systems Medicine, University of Rome "Tor Vergata", Via Montpellier 1, 00133 Rome, Italy.
authors: Maria Laura
authors: ML
authors: Cupi
authors: *Department of Systems Medicine, University of Rome "Tor Vergata", Via Montpellier 1, 00133 Rome, Italy.
authors: Pamela
authors: P
authors: Mancia
authors: †Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.
authors: Flavio
authors: F
authors: Caprioli
authors: *Department of Systems Medicine, University of Rome "Tor Vergata", Via Montpellier 1, 00133 Rome, Italy.
authors: Irene
authors: I
authors: Marafini
authors: *Department of Systems Medicine, University of Rome "Tor Vergata", Via Montpellier 1, 00133 Rome, Italy.
authors: Alfredo
authors: A
authors: Colantoni
authors: *Department of Systems Medicine, University of Rome "Tor Vergata", Via Montpellier 1, 00133 Rome, Italy.
authors: Angela
authors: A
authors: Ortenzi
authors: *Department of Systems Medicine, University of Rome "Tor Vergata", Via Montpellier 1, 00133 Rome, Italy.
authors: Federica
authors: F
authors: Laudisi
authors: ‡Department of Surgery, University "Tor Vergata", Via Montpellier 1, 00133 Rome, Italy.
authors: Giuseppe
authors: G
authors: Sica
authors: ‡Department of Surgery, University "Tor Vergata", Via Montpellier 1, 00133 Rome, Italy.
authors: PierPaolo
authors: P
authors: Sileri
authors: *Department of Systems Medicine, University of Rome "Tor Vergata", Via Montpellier 1, 00133 Rome, Italy.
authors: Francesco
authors: F
authors: Pallone
authors: *Department of Systems Medicine, University of Rome "Tor Vergata", Via Montpellier 1, 00133 Rome, Italy.
authors: Giovanni
authors: G
authors: Monteleone
mesh_terms: D003093:Colitis, Ulcerative / Q000276:immunology / Q000378:metabolism*; D003424:Crohn Disease / Q000235:genetics / Q000378:metabolism*; D019858:Enteroendocrine Cells / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000276:immunology; D007378:Interleukins / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000276:immunology; D008264:Macrophages / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C529076:IL34 protein, human; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha