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.
Franzè, E., Marafini, I., De Simone, V., Monteleone, I., Caprioli, F., Colantoni, A., et al. (2016). Interleukin-34 induces Cc-chemokine ligand 20 in gut epithelial cells. JOURNAL OF CROHN'S AND COLITIS, 10(1), 87-94.
|Tipologia:||Articolo su rivista|
|Citazione:||Franzè, E., Marafini, I., De Simone, V., Monteleone, I., Caprioli, F., Colantoni, A., et al. (2016). Interleukin-34 induces Cc-chemokine ligand 20 in gut epithelial cells. JOURNAL OF CROHN'S AND COLITIS, 10(1), 87-94.|
|Settore Scientifico Disciplinare:||Settore MED/12 - Gastroenterologia|
|Revisione (peer review):||Esperti anonimi|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1093/ecco-jcc/jjv181|
|Stato di pubblicazione:||Pubblicato|
|Data di pubblicazione:||2016|
|Titolo:||Interleukin-34 induces Cc-chemokine ligand 20 in gut epithelial cells|
|Autori:||Franzè, E; Marafini, I; De Simone, V; Monteleone, I; Caprioli, F; Colantoni, A; Ortenzi, A; Crescenzi, F; Izzo, R; Sica, G; Sileri, P; Rossi, P; Pallone, F; Monteleone, G|
|Appare nelle tipologie:||01 - Articolo su rivista|