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- Title
Interleukin-25 production is differently regulated by TNF-α and TGF-β1 in the human gut.
- Authors
Fina, D.; Franzè, E.; Rovedatti, L.; Corazza, G. R.; Biancone, L.; Sileri, P. P.; Sica, G.; MacDonald, T. T.; Pallone, F.; Di Sabatino, A.; Monteleone, G.
- Abstract
An altered balance between effector and regulatory factors is supposed to sustain the tissue-damaging immune response in inflammatory bowel disease (IBD). We have recently shown that in IBD, there is a defective synthesis of the counter-regulatory cytokine, interleukin (IL)-25. In this study we investigated factors that control IL-25 production in the gut. IBD patients produced less IL-25 when compared with normal controls. Stimulation of normal intestinal explants with tumor necrosis factor-α (TNF-α), but not interferon-γ (IFN-γ) or IL-21, reduced IL-25 synthesis. Consistently, IL-25 production was enhanced by anti-TNF-α both in vitro and in vivo. Upregulation of IL-25 was also seen in normal colonic explants stimulated with transforming growth factor-β1 (TGF-β1). As in IBD, TGF-β1 activity is abrogated by Smad7, we next assessed whether inhibition of Smad7 with an antisense oligonucleotide enhanced IL-25 expression. Knockdown of Smad7 was accompanied by an increase in IL-25 production. Data show that IL-25 production is differently regulated by TNF-α and TGF-β1 in the human gut.
- Subjects
INFLAMMATORY bowel diseases; TUMOR necrosis factors; CELLULAR immunity; TRANSFORMING growth factors; OLIGONUCLEOTIDES
- Publication
Mucosal Immunology (1933-0219), 2011, Vol 4, Issue 2, p239
- ISSN
1933-0219
- Publication type
Article
- DOI
10.1038/mi.2010.68