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.
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: Maria A Battistone; Raul German Spallanzani; Alexandra C Mendelsohn; Diane Capen; Anil V Nair; Dennis Brown; Sylvie Breton Journal: J Cell Sci Date: 2019-11-18 Impact factor: 5.285
Authors: Ahmed Al-Dwairi; Mohammad Alqudah; Othman Al-Shboul; Mahmoud Alfaqih; Dana Alomari Journal: Exp Ther Med Date: 2018-05-25 Impact factor: 2.447
Authors: Stephanie Zwicker; Daniela Bureik; Madeleen Bosma; Gisele Lago Martinez; Sven Almer; Elisabeth A Boström Journal: PLoS One Date: 2016-11-29 Impact factor: 3.240
Authors: Bert K Lopansri; Daniel T Leung; Robert Schlaberg; Amanda Barrett; Kornelia Edes; Michael Graves; Litty Paul; Jenna Rychert Journal: Pathog Immun Date: 2018-09-12