| Autor: |
Tinoco-Veras, Christianne Maria, Santos, Ana Angélica Q. A., Stipursky, Joice, Meloni, Marcelo, Araujo, Ana Paula Bérgamo, Foschetti, Danielle Abreu, López-Ureña, Diana, Quesada-Gómez, Carlos, Leitão, Renata F. C., Gomes, Flávia Carvalho Alcantara, Brito, Gerly Anne de Castro |
| Zdroj: |
Infection and Immunity; July 2017, Vol. 85 Issue: 10 |
| Abstrakt: |
ABSTRACTClostridium 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 β (TGF-β) 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-β1, which has a protective effect on epithelial resistance and a TcdA/TGF-β signaling pathway interaction. The activation of this pathway in vivohas not been elucidated. The aim of this study was to investigate the role of the TGF-β1 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-β1 and its receptor, TβRII, in vitroand in vivo. TcdA induced nuclear translocation of the transcription factors SMAD2/3, a hallmark of TGF-β1 pathway activation, both in IEC cells and in mouse ileal tissue. The addition of recombinant TGF-β1 (rTGF-β) 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-β1 signaling pathway activation and suggest that this pathway might play a protective role against the effect of C. difficile-toxin. |
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