BACKGROUND: Presentation after Clostridium difficile infection may depend on the level of epithelial exposure to toxins. We investigated epithelial barrier function and expression of interleukin (IL)-8 and transforming growth factor (TGF)-beta in response to varying concentrations of C. difficile toxin A. METHODS: T84 cells were either preexposed or continuously exposed to C. difficile toxin A (0.01-1000 ng/mL). Barrier function was assessed by measurements of transepithelial electrical resistance. RESULTS: Preexposure to < or =10 ng/mL toxin A led to an increase in the release of TGF-beta 1, but there was no change in the expression of IL-8. In contrast, after preexposure to >10 ng/mL toxin A, there was enhanced expression of IL-8, but release of TGF-beta 1 was similar to that in control monolayers. After preexposure to >10 ng/mL toxin A, there was complete and irreversible loss of electrical resistance. At lower concentrations, loss of resistance across monolayers was followed by recovery, which was enhanced by all 3 recombinant isoforms of TGF-beta. Pretreatment with recombinant isoforms of TGF-beta or coculture with TGF-beta 3-expressing colonic subepithelial myofibroblasts was also protective. CONCLUSIONS: In C. difficile infection, the development and severity of colonic inflammation may depend on the exposure of intestinal epithelial cells to toxins and the expression of proinflammatory (IL-8) and protective (TGF-beta) factors.
BACKGROUND: Presentation after Clostridium difficileinfection may depend on the level of epithelial exposure to toxins. We investigated epithelial barrier function and expression of interleukin (IL)-8 and transforming growth factor (TGF)-beta in response to varying concentrations of C. difficile toxin A. METHODS: T84 cells were either preexposed or continuously exposed to C. difficile toxin A (0.01-1000 ng/mL). Barrier function was assessed by measurements of transepithelial electrical resistance. RESULTS: Preexposure to < or =10 ng/mL toxin A led to an increase in the release of TGF-beta 1, but there was no change in the expression of IL-8. In contrast, after preexposure to >10 ng/mL toxin A, there was enhanced expression of IL-8, but release of TGF-beta 1 was similar to that in control monolayers. After preexposure to >10 ng/mL toxin A, there was complete and irreversible loss of electrical resistance. At lower concentrations, loss of resistance across monolayers was followed by recovery, which was enhanced by all 3 recombinant isoforms of TGF-beta. Pretreatment with recombinant isoforms of TGF-beta or coculture with TGF-beta 3-expressing colonic subepithelial myofibroblasts was also protective. CONCLUSIONS: In C. difficileinfection, the development and severity of colonic inflammation may depend on the exposure of intestinal epithelial cells to toxins and the expression of proinflammatory (IL-8) and protective (TGF-beta) factors.
Authors: Jun Huang; Ciarán P Kelly; Kyriaki Bakirtzi; Javier A Villafuerte Gálvez; Dena Lyras; Steven J Mileto; Sarah Larcombe; Hua Xu; Xiaotong Yang; Kelsey S Shields; Weishu Zhu; Yi Zhang; Jeffrey D Goldsmith; Ishan J Patel; Joshua Hansen; Meijin Huang; Seppo Yla-Herttuala; Alan C Moss; Daniel Paredes-Sabja; Charalabos Pothoulakis; Yatrik M Shah; Jianping Wang; Xinhua Chen Journal: Nat Microbiol Date: 2018-12-03 Impact factor: 17.745
Authors: Simon A Hirota; Kyla Fines; Jeffrey Ng; Danya Traboulsi; Josh Lee; Eikichi Ihara; Yan Li; William G Willmore; Daniel Chung; Melanie M Scully; Thomas Louie; Shaun Medlicott; Manigandan Lejeune; Kris Chadee; Glen Armstrong; Sean P Colgan; Daniel A Muruve; Justin A MacDonald; Paul L Beck Journal: Gastroenterology Date: 2010-03-27 Impact factor: 22.682
Authors: S W Pawlowski; G Calabrese; G L Kolling; J Platts-Mills; R Freire; C AlcantaraWarren; B Liu; R B Sartor; R L Guerrant Journal: J Infect Dis Date: 2010-10-26 Impact factor: 5.226
Authors: Christianne Maria Tinoco-Veras; Ana Angélica Q A Santos; Joice Stipursky; Marcelo Meloni; Ana Paula Bérgamo Araujo; Danielle Abreu Foschetti; Diana López-Ureña; Carlos Quesada-Gómez; Renata F C Leitão; Flávia Carvalho Alcantara Gomes; Gerly Anne de Castro Brito Journal: Infect Immun Date: 2017-09-20 Impact factor: 3.441
Authors: Andressa A F L Maciel; Reinaldo B Oriá; Manuel B Braga-Neto; Andréa B Braga; Eunice B Carvalho; Herene B M Lucena; Gerly A C Brito; Richard L Guerrant; Aldo A M Lima Journal: Toxicon Date: 2007-07-31 Impact factor: 3.033