Interleukin-25 production is differently regulated by TNF-α and TGF-ß1 in the human gut.
Mucosal Immunol
; 4(2): 239-44, 2011 Mar.
Article
in En
| MEDLINE
| ID: mdl-20944558
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-ß1 (TGF-ß1). As in IBD, TGF-ß1 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-ß1 in the human gut.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Gene Expression Regulation
/
Tumor Necrosis Factor-alpha
/
Interleukin-17
/
Transforming Growth Factor beta1
/
Intestinal Mucosa
Limits:
Humans
Language:
En
Journal:
Mucosal Immunol
Journal subject:
ALERGIA E IMUNOLOGIA
Year:
2011
Document type:
Article
Affiliation country:
Italia