| RRC ID |
52411
|
| 著者 |
Seike S, Takehara M, Takagishi T, Miyamoto K, Kobayashi K, Nagahama M.
|
| タイトル |
Delta-toxin from Clostridium perfringens perturbs intestinal epithelial barrier function in Caco-2 cell monolayers.
|
| ジャーナル |
Biochim Biophys Acta Biomembr
|
| Abstract |
Clostridium perfringens delta-toxin is a β-barrel-pore-forming toxin (β-PFT) and a presumptive virulence factor of type B and C strains, which are causative organisms of fatal intestinal diseases in animals. We showed previously that delta-toxin causes cytotoxicity via necrosis in sensitive cells. Here, we examined the effect of delta-toxin on intestinal membrane integrity. Delta-toxin led to a reduction in transepithelial electrical resistance (TEER) and increased the permeability of fluorescence isothiocyanate-conjugated dextran in human intestinal epithelial Caco-2 cells without changing the tight junction proteins, such as zonula occludens-1 (ZO-1), occludin, and claudin-1. On the other hand, delta-toxin reduced the cellular levels of adherence junction protein E-cadherin before cell injury. A disintegrin and metalloprotease (ADAM) 10 facilitates E-cadherin cleavage and was identified as the cellular receptor for alpha-toxin, a β-PFT produced by Staphylococcus aureus. ADAM10 inhibitor (GI254023X) blocked the toxin-induced decrease in TEER and cleavage of E-cadherin. Delta-toxin enhanced ADAM10 activity in a dose- and time-dependent manner. Furthermore, delta-toxin colocalized with ADAM10. These results indicated that ADAM10 plays a key role in delta-toxin-induced intestinal injury.
|
| 巻・号 |
1860(2)
|
| ページ |
428-433
|
| 公開日 |
2018-2-1
|
| DOI |
10.1016/j.bbamem.2017.10.003
|
| PII |
S0005-2736(17)30313-9
|
| PMID |
28988777
|
| MeSH |
ADAM10 Protein / metabolism
Bacterial Toxins / pharmacology*
Caco-2 Cells
Cadherins / metabolism
Cell Membrane Permeability / drug effects*
Claudin-1 / metabolism
Dose-Response Relationship, Drug
Epithelial Cells / drug effects*
Epithelial Cells / metabolism
Humans
Immunoblotting
Intestinal Mucosa / drug effects*
Intestinal Mucosa / metabolism
Occludin / metabolism
Time Factors
Zonula Occludens-1 Protein / metabolism
|
| IF |
3.79
|
| 引用数 |
6
|
| リソース情報 |
| ヒト・動物細胞 |
CACO-2(RCB0988) |
