Mice with targeted disruptions of the transforming growth factor-beta1 (TGF-beta1) gene or TGF-beta1 intracellular signalling pathways develop intestinal inflammation. Conversely, TGF-beta1-producing regulatory T cells protect against experimental colitis. Paradoxically, however, TGF-beta1 production is high in the gut of patients with chronic inflammatory intestinal disease, and yet inflammation proceeds unchecked. Here we discuss the functional role of Smad7, an intracellular inhibitor of TGF-beta1 signalling, in the control of gut inflammation by TGF-beta1. In particular, we delineate a scenario in which the high expression of Smad7 in inflammatory cells renders them unresponsive to TGF-beta1 and propose that control of Smad7, not TGF-beta1 production, is a key determinant in understanding how TGF-beta1 negatively regulates gut inflammation.

Monteleone, G., Pallone, F., Macdonald, T. (2004). Smad7 in TGF-beta-mediated negative regulation of gut inflammation. TRENDS IN IMMUNOLOGY, 25(10), 513-517 [10.1016/j.it.2004.07.008].

Smad7 in TGF-beta-mediated negative regulation of gut inflammation

MONTELEONE, GIOVANNI;PALLONE, FRANCESCO;
2004-01-01

Abstract

Mice with targeted disruptions of the transforming growth factor-beta1 (TGF-beta1) gene or TGF-beta1 intracellular signalling pathways develop intestinal inflammation. Conversely, TGF-beta1-producing regulatory T cells protect against experimental colitis. Paradoxically, however, TGF-beta1 production is high in the gut of patients with chronic inflammatory intestinal disease, and yet inflammation proceeds unchecked. Here we discuss the functional role of Smad7, an intracellular inhibitor of TGF-beta1 signalling, in the control of gut inflammation by TGF-beta1. In particular, we delineate a scenario in which the high expression of Smad7 in inflammatory cells renders them unresponsive to TGF-beta1 and propose that control of Smad7, not TGF-beta1 production, is a key determinant in understanding how TGF-beta1 negatively regulates gut inflammation.
2004
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore MED/12 - GASTROENTEROLOGIA
English
cadherin; immunoglobulin enhancer binding protein; interleukin 7; mitogen activated protein kinase; mitogen activated protein kinase p38; phosphatidylinositol 3 kinase; protein c jun; Rac protein; Raf protein; Ras protein; RhoA guanine nucleotide binding protein; Smad2 protein; Smad3 protein; Smad4 protein; Smad7 protein; STAT1 protein; stress activated protein kinase; transcription factor; transforming growth factor beta1; tumor necrosis factor alpha; cell infiltration; colitis; Crohn disease; cytokine production; enteritis; gene deletion; human; immunological tolerance; inflammatory cell; intestine flora; mononuclear cell; mucosal immunity; nonhuman; protein analysis; protein degradation; protein expression; protein function; protein induction; protein localization; protein protein interaction; review; signal transduction; Th1 cell; transcription regulation; ubiquitination; upregulation; Animals; DNA-Binding Proteins; Humans; Inflammation; Intestinal Mucosa; Intestines; Signal Transduction; Smad7 Protein; Trans-Activators; Transforming Growth Factor beta
Monteleone, G., Pallone, F., Macdonald, T. (2004). Smad7 in TGF-beta-mediated negative regulation of gut inflammation. TRENDS IN IMMUNOLOGY, 25(10), 513-517 [10.1016/j.it.2004.07.008].
Monteleone, G; Pallone, F; Macdonald, T
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/28773
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