alexa Abstract | Smad7 as a Target for Immunomodulation Strategy in Inflammatory Bowel Diseases
ISSN: 1745-7580

Immunome Research
Open Access

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Abstract

Inflammatory bowel diseases (IBD) are chronic inflammatory pathologies of the gut, characterized by a relapsing-remitting course. Although IBD pathogenesis is not fully understood, epidemiological and experimental data suggest that multiple environmental factors can, in genetically predisposed individuals, trigger an excessive immune response directed against the antigens of the normal intestinal microflora, which eventually leads to the tissue damage. Defects in the physiological mechanisms/factors of counter-regulation contribute to amplify and sustain such a detrimental response. For instance, in inflamed tissue of IBD patients there is diminished activity of the immunesuppressive cytokine transforming growth factor (TGF)-β1, due to elevated levels of Smad7, an intracellular inhibitor of TGF-β1 signaling. Consistently, knockdown of Smad7 with a specific antisense oligonucleotide suppresses inflammatory signals in cultured intestinal cells of IBD patients and in the gut of mice with IBD-like experimental colitis. Moreover, treatment of patients with active Crohn’s disease, one of the two major IBD in human beings, with Mongersen, an oral compound containing Smad7 antisense oligonucleotide, is accompanied by induction of clinical remission. Altogether these data indicate that targeting Smad7 represents a promising approach to modulate the ongoing mucosal inflammation in IBD.

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Author(s): Silvia Sedda, Edoardo Troncone, Maria Imeneo and Giovanni Monteleone

Keywords

Crohn&rsquo,s disease, Ulcerative colitis, Counter-regulatory mechanisms, Transforming growth factor-&beta,1, Mucosal inflammation, Crohn?s disease, Ulcerative colitis, Counter-regulatory mechanisms, Transforming growth factor-?1, Mucosal inflammation

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