scholarly journals Clostridium difficile toxin A-mediated Caco-2 barrier damage was attenuated by insect-derived fractions and corresponded to increased gene transcription of cell junctional and proliferation proteins

2021 ◽  
Author(s):  
Liyou Dong ◽  
Coen Govers ◽  
Monic Tomassen ◽  
Renata M.C Ariens ◽  
Els Oosterink ◽  
...  
Keyword(s):  
Clostridium Difficile ◽  
Gene Transcription ◽  
Intestinal Epithelial ◽  
Epithelial Layer ◽  
Toxin A ◽  
Clostridium Difficile Toxin ◽  
Clostridium Difficile Toxin A

Pathogenesis of C. difficile in the intestine is associated with the secretion of toxins which can damage the intestinal epithelial layer and result in disease, such as diarrhoea. Treatment for...

Protective role of HSP72 against Clostridium difficile toxin A-induced intestinal epithelial cell dysfunction

2003 ◽  
Vol 284 (4) ◽  
pp. C1073-C1082 ◽  
Author(s):  
Tom S. Liu ◽  
Mark W. Musch ◽  
Kazunori Sugi ◽  
Margaret M. Walsh-Reitz ◽  
Mark J. Ropeleski ◽  
...  
Keyword(s):  
Clostridium Difficile ◽  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Atp Release ◽  
Protective Role ◽  
Atp Depletion ◽  
Intestinal Epithelial ◽  
Toxin A ◽  
Clostridium Difficile Toxin ◽  
Clostridium Difficile Toxin A

We determined whether the cytoprotective heat shock protein HSP72 protects against the injurious effects of Clostridium difficile toxin A (TxA) on intestinal epithelial cells. Colonic epithelial Caco-2/bbe (C2) cells were stably transfected with HSP72 antisense (C2AS) or vector only (C2VC), resulting in low and high HSP72 expression, respectively. Measurements of epithelial barrier integrity, mitochondrial function, and apoptosis activation were assessed after TxA exposure. HSP72 and RhoA interactions were evaluated with immunoprecipitations. In C2AS cells, TxA was associated with a greater decrease in transepithelial resistance (TER), an increase in [3H]mannitol flux, and increased dissociation of perijunctional actin. Although HSP72 binds RhoA, it failed to prevent RhoA glucosylation. TxA caused a more rapid decrease in ATP, release of cytochrome c, and activation of caspase-9 in C2AS cells. To determine whether ATP depletion decreases TER, we treated cells with antimycin A, which caused a decline in TER. We conclude that HSP72 may protect intestinal epithelial cells from TxA-mediated damage through several mechanisms, including actin stabilization, mitochondrial protection, and inhibition of apoptosis activation, but not by prevention of RhoA glucosylation.

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