کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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3296315 | 1209867 | 2007 | 10 صفحه PDF | دانلود رایگان |
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-3α 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-3α), a T-cell chemoattractant. Inhibition of ERK1/2 but not p38 suppressed IL-21–induced MIP-3α production. IL-21–treated cell culture supernatants enhanced in vitro lymphocyte migration, and this effect was inhibited by anti-MIP-3α antibody. Treatment of IBD explants with anti–IL-21 reduced MIP-3α 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.
Journal: Gastroenterology - Volume 132, Issue 1, January 2007, Pages 166–175