Clostridium perfringens Epsilon-Toxin Impairs the Barrier Function in MDCK Cell Monolayers in a [Ca.sup.2+]-Dependent Manner

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-t...

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Bibliographic Details
Published inToxins Vol. 10; no. 5; p. 1
Main Authors Nagahama, Masahiro, Seike, Soshi, Ochi, Sadayuki, Kobayashi, Keiko, Takehara, Masaya
Format Journal Article
LanguageEnglish
Published MDPI AG 01.05.2020
Subjects
Clostridium infections
Development and progression
Diagnosis
Epithelial cells
Physiological aspects
Toxins
Japan
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Summary: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-l,4,5-triphosphate (IP3). U73122 blocked the formation of DAG and IP3 induced by the toxin. Epsilon-toxin also specifically activated endogenous PLC-[gamma]I. Epsilon-toxin dose-dependently increased the cytosolic calcium ion concentration ([Ca.sup.2+]i). The toxin-induced elevation of [Ca.sup.2+]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 [Ca.sup.2+] influx through activating the phosphorylation of PLC-[gamma]I and then causes TJ opening accompanied by cofilin dephosphorylation.
ISSN:2072-6651
2072-6651
DOI:10.3390/toxinsl2050286