alexa Smad7 Sustains Inflammation in the Gut: From Bench to Bedside
ISSN: 2155-9899

Journal of Clinical & Cellular Immunology
Open Access

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Review Article

Smad7 Sustains Inflammation in the Gut: From Bench to Bedside

Irene Marafini, Silvia Sedda, Davide Di Fusco, Michele M Figliuzzi, Francesco Pallone and Giovanni Monteleone*
Department of Systems Medicine, University of Rome Tor Vergata, Italy
Corresponding Author : Giovanni Monteleone
Department of Systems Medicine
University of Rome Tor Vergata
Via Montpellier 1, 00133 Rome, Italy Tel: +39.06.72596158
Fax: +39.06.72596391
Received April 29, 2014; Accepted July 09, 2014; Published July 16, 2014
Citation: Marafini I, Sedda S, Di Fusco D, Figliuzzi MM, Pallone F, et al. (2014) Smad7 Sustains Inflammation in the Gut: From Bench to Bedside. J Clin Cell Immunol 5:236. doi: 10.4172/2155-9899.1000236
Copyright: © 2014 Marafini I, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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In Crohn’s disease (CD) and ulcerative colitis (UC), the two major forms of inflammatory bowel disease (IBD) in human beings, the pathological process is driven by an excessive immune response that is directed against components of the luminal flora and inappropriately controlled by immunesuppressive mechanisms. One such a mechanism involves TGF-β1, a pleiotropic cytokine that targets both immune and non-immune cells in the gut. TGF- β1 is highly expressed in inflamed mucosa of IBD patients but paradoxically it is unable to activate Smad-associated intracellular signalling and suppress inflammatory cytokine responses. This is because IBD-related inflammation is marked by elevated levels of Smad7, an inhibitor of TGF-β1 signalling. Consistently, knockdown of Smad7 with a specific antisense oligonucleotide restores TGF-β1 function, inhibits inflammatory cytokine production, and ameliorates colitis in mice. In this article we review the available data supporting the pathogenic role of Smad7 in gut as well as the results of a recent phase 1 trial assessing the safety and tolerability of a Smad7 antisense oligonucleotide in CD patients.


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