Transforming Growth Factor ß1/SMAD Signaling Pathway Activation Protects the Intestinal Epithelium from Clostridium difficile Toxin A-Induced Damage.
Infect Immun
; 85(10)2017 10.
Article
em En
| MEDLINE
| ID: mdl-28784928
ABSTRACT
Clostridium difficile, the main cause of diarrhea in hospitalized patients, produces toxins A (TcdA) and B (TcdB), which affect intestinal epithelial cell survival, proliferation, and migration and induce an intense inflammatory response. Transforming growth factor ß (TGF-ß) is a pleiotropic cytokine affecting enterocyte and immune/inflammatory responses. However, it has been shown that exposure of intestinal epithelium to a low concentration of TcdA induces the release of TGF-ß1, which has a protective effect on epithelial resistance and a TcdA/TGF-ß signaling pathway interaction. The activation of this pathway in vivo has not been elucidated. The aim of this study was to investigate the role of the TGF-ß1 pathway in TcdA-induced damage in a rat intestinal epithelial cell line (IEC-6) and in a mouse model of an ileal loop. TcdA increased the expression of TGF-ß1 and its receptor, TßRII, in vitro and in vivo TcdA induced nuclear translocation of the transcription factors SMAD2/3, a hallmark of TGF-ß1 pathway activation, both in IEC cells and in mouse ileal tissue. The addition of recombinant TGF-ß1 (rTGF-ß) prevented TcdA-induced apoptosis/necrosis and restored proliferation and repair activity in IEC-6 cells in the presence of TcdA. Together, these data show that TcdA induces TGF-ß1 signaling pathway activation and suggest that this pathway might play a protective role against the effect of C. difficile-toxin.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Toxinas Bacterianas
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Transdução de Sinais
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Enterotoxinas
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Proteínas Smad
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Fator de Crescimento Transformador beta1
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Mucosa Intestinal
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Infect Immun
Ano de publicação:
2017
Tipo de documento:
Article