Author(s): 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 Ferreira de Carvalho ; Gomes, Flávia Carvalho Alcantara ; Brito, Gerly Anne de Castro
Date: 2017
Origin: Oasisbr
Subject(s): Clostridium difficile; Mucosa Intestinal; Intestinal Mucosa
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. Trans- forming growth factor (TGF- ) is a pleiotropic cytokine affecting enterocyte and immune/inflammatory responses. However, it has been shown that exposure of in- testinal epithelium to a low concentration of TcdA induces the release of TGF- 1, which has a protective effect on epithelial resistance and a TcdA/TGF- 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- 1 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- 1 and its receptor, T RII, in vitro and in vivo . TcdA induced nuclear translocation of the transcription factors SMAD2/3, a hallmark of TGF- 1 pathway activation, both in IEC cells and in mouse ileal tissue. The addition of recombinant TGF- 1 (rTGF- ) 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- 1 signaling pathway activation and suggest that this pathway might play a protective role against the effect of C. difficile -toxin.
