Interleukin-25 production is differently regulated by TNF-α and TGF-β1 in the human gut

D. Fina, E. Franzè, L. Rovedatti, G. R. Corazza, L. Biancone, P. P. Sileri, G. Sica, T. T. MacDonald, F. Pallone, A. Di Sabatino, G. Monteleone

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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.

Original languageEnglish
Pages (from-to)239-244
Number of pages6
JournalMucosal Immunology
Volume4
Issue number2
DOIs
Publication statusPublished - Mar 2011

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ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

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. (2011). Interleukin-25 production is differently regulated by TNF-α and TGF-β1 in the human gut. Mucosal Immunology, 4(2), 239-244. https://doi.org/10.1038/mi.2010.68