Background & Aims: Interleukin (IL)-21, a T-cell-derived cytokine, is produced in excess in inflammatory bowel diseases (IBD). The IL-21 receptor (IL-21R) is expressed by immune and nonimmune cells, raising the possibility that IL-21 has broad effects in gut inflammation. In this study we examined whether intestinal epithelial cells express IL-21R and respond to IL-21 in IBD. Methods: IL-21R was evaluated in intestinal samples of IBD patients and controls by immunohistochemistry and Western blotting. Intestinal epithelial cells were stimulated with IL-21, and cell-free supernatants were evaluated by a protein array and enzyme-linked immunosorbent assay. The effect of IL-21-treated epithelial cell supernatants on blood lymphocyte migration was assessed using a chemotaxis assay. Finally, we evaluated the effect of a neutralizing IL-21 antibody on MIP-3 alpha synthesis in ex vivo organ cultures of IBD mucosal explants. Results: Constitutive expression of IL-21R was seen in intestinal epithelial cells, but was higher in IBD patients than in controls. Stimulation of intestinal epithelial cells with IL-21 resulted in enhanced phosphorylation of ERK1/2 and p38 and increased synthesis of macrophage inflammatory protein-3 alpha (MIP-3 alpha), a T-cell chemoattractant. Inhibition of ERK1/2 but not p38 suppressed IL-21-induced MIP-3 alpha production. IL-21-treated cell culture supernatants enhanced in vitro lymphocyte migration, and this effect was inhibited by anti-MIP-3 alpha antibody. Treatment of IBD explants with anti-IL-21 reduced MIP-3 alpha production. Conclusions: These data show that intestinal epithelial cells are a target of IL-21 and that IL-21 is involved in the cross-talk between epithelial and immune cells in the gut.

Caruso, R., Fina, D., Peluso, I., Stolfi, C., Fantini, M.c., Gioia, V., et al. (2007). A functional role for interleukin-21 in promoting the synthesis of the T-cell chemoattractant, MIP-3 alpha, by gut epithelial cells. GASTROENTEROLOGY, 132(1), 166-175 [10.1053/j.gastro.2006.09.053].

A functional role for interleukin-21 in promoting the synthesis of the T-cell chemoattractant, MIP-3 alpha, by gut epithelial cells

Stolfi C.;FANTINI, MASSIMO CLAUDIO;DEL VECCHIO BLANCO, GIOVANNA;PALLONE, FRANCESCO;MONTELEONE, GIOVANNI
2007-01-01

Abstract

Background & Aims: Interleukin (IL)-21, a T-cell-derived cytokine, is produced in excess in inflammatory bowel diseases (IBD). The IL-21 receptor (IL-21R) is expressed by immune and nonimmune cells, raising the possibility that IL-21 has broad effects in gut inflammation. In this study we examined whether intestinal epithelial cells express IL-21R and respond to IL-21 in IBD. Methods: IL-21R was evaluated in intestinal samples of IBD patients and controls by immunohistochemistry and Western blotting. Intestinal epithelial cells were stimulated with IL-21, and cell-free supernatants were evaluated by a protein array and enzyme-linked immunosorbent assay. The effect of IL-21-treated epithelial cell supernatants on blood lymphocyte migration was assessed using a chemotaxis assay. Finally, we evaluated the effect of a neutralizing IL-21 antibody on MIP-3 alpha synthesis in ex vivo organ cultures of IBD mucosal explants. Results: Constitutive expression of IL-21R was seen in intestinal epithelial cells, but was higher in IBD patients than in controls. Stimulation of intestinal epithelial cells with IL-21 resulted in enhanced phosphorylation of ERK1/2 and p38 and increased synthesis of macrophage inflammatory protein-3 alpha (MIP-3 alpha), a T-cell chemoattractant. Inhibition of ERK1/2 but not p38 suppressed IL-21-induced MIP-3 alpha production. IL-21-treated cell culture supernatants enhanced in vitro lymphocyte migration, and this effect was inhibited by anti-MIP-3 alpha antibody. Treatment of IBD explants with anti-IL-21 reduced MIP-3 alpha production. Conclusions: These data show that intestinal epithelial cells are a target of IL-21 and that IL-21 is involved in the cross-talk between epithelial and immune cells in the gut.
2007
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/12 - GASTROENTEROLOGIA
Settore BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA
English
chemoattractant; interleukin 21; interleukin 21 receptor; macrophage inflammatory protein 3alpha; mitogen activated protein kinase 1; mitogen activated protein kinase 3; mitogen activated protein kinase p38; neutralizing antibody; article; cell culture; chemotaxis; clinical article; controlled study; enteritis; enzyme linked immunosorbent assay; epithelium cell; ex vivo study; explant; human; human cell; human tissue; immunohistochemistry; intestine epithelium; intestine epithelium cell; intestine mucosa; lymphocyte; lymphocyte migration; organ culture; priority journal; protein analysis; protein function; protein synthesis; supernatant; T lymphocyte; Western blotting; Antibodies; Caco-2 Cells; Cell Communication; Cell Movement; Chemokines, CC; Colon; Epithelial Cells; HT29 Cells; Humans; Inflammatory Bowel Diseases; Interleukins; Intestinal Mucosa; Macrophage Inflammatory Proteins; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Organ Culture Techniques; Receptors, Interleukin-21; T-Lymphocytes
Caruso, R., Fina, D., Peluso, I., Stolfi, C., Fantini, M.c., Gioia, V., et al. (2007). A functional role for interleukin-21 in promoting the synthesis of the T-cell chemoattractant, MIP-3 alpha, by gut epithelial cells. GASTROENTEROLOGY, 132(1), 166-175 [10.1053/j.gastro.2006.09.053].
Caruso, R; Fina, D; Peluso, I; Stolfi, C; Fantini, Mc; Gioia, V; Caprioli, F; DEL VECCHIO BLANCO, G; Paoluzi, Oa; Macdonald, Tt; Pallone, F; Monteleone, G
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/28248
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