RRC ID 62835
著者 Nagahama M, Seike S, Ochi S, Kobayashi K, Takehara M.
タイトル Clostridium perfringens Epsilon-Toxin Impairs the Barrier Function in MDCK Cell Monolayers in a Ca2+-Dependent Manner.
ジャーナル Toxins (Basel)
Abstract Epsilon-toxin produced by Clostridium perfringens significantly contributes to the pathogeneses of enterotoxemia in ruminants and multiple sclerosis in humans. Epsilon-toxin forms a heptameric oligomer in the host cell membrane, promoting cell disruption. Here, we investigate the effect of epsilon-toxin on epithelial barrier functions. Epsilon-toxin impairs the barrier integrity of Madin-Darby Canine Kidney (MDCK) cells, as demonstrated by decreased transepithelial electrical resistance (TEER), increased paracellular flux marker permeability, and the decreased cellular localization of junctional proteins, such as occludin, ZO-1, and claudin-1. U73122, an endogenous phospholipase C (PLC) inhibitor, inhibited the decrease in TEER and the increase in the permeability of flux marker induced by epsilon-toxin. The application of epsilon-toxin to MDCK cells resulted in the biphasic formation of 1,2-diacylglycerol (DAG) and inositol-1,4,5-triphosphate (IP3). U73122 blocked the formation of DAG and IP3 induced by the toxin. Epsilon-toxin also specifically activated endogenous PLC-γ1. Epsilon-toxin dose-dependently increased the cytosolic calcium ion concentration ([Ca2+]i). The toxin-induced elevation of [Ca2+]i was inhibited by U73122. Cofilin is a key regulator of actin cytoskeleton turnover and tight-junction (TJ) permeability regulation. Epsilon-toxin caused cofilin dephosphorylation. These results demonstrate that epsilon-toxin induces Ca2+ influx through activating the phosphorylation of PLC-γ1 and then causes TJ opening accompanied by cofilin dephosphorylation.
巻・号 12(5)
公開日 2020-4-30
DOI 10.3390/toxins12050286
PII toxins12050286
PMID 32365779
PMC PMC7291203
MeSH Actin Depolymerizing Factors / metabolism Animals Bacterial Toxins / toxicity* Calcium / metabolism* Calcium Signaling / drug effects* Dogs Electric Impedance Epithelial Cells / drug effects* Epithelial Cells / metabolism Epithelial Cells / pathology Madin Darby Canine Kidney Cells Permeability Phospholipase C gamma / metabolism Phosphorylation Tight Junctions / drug effects* Tight Junctions / metabolism Tight Junctions / pathology
IF 3.531
リソース情報
ヒト・動物細胞 MDCK(RCB0995)