| RRC ID |
44543
|
| 著者 |
Nagahama M, Shibutani M, Seike S, Yonezaki M, Takagishi T, Oda M, Kobayashi K, Sakurai J.
|
| タイトル |
The p38 MAPK and JNK pathways protect host cells against Clostridium perfringens beta-toxin.
|
| ジャーナル |
Infect Immun
|
| Abstract |
Clostridium perfringens beta-toxin is an important agent of necrotic enteritis and enterotoxemia. Beta-toxin is a pore-forming toxin (PFT) that causes cytotoxicity. Two mitogen-activated protein kinase (MAPK) pathways (p38 and c-Jun N-terminal kinase [JNK]-like) provide cellular defense against various stresses. To investigate the role of the MAPK pathways in the toxic effect of beta-toxin, we examined cytotoxicity in five cell lines. Beta-toxin induced cytotoxicity in cells in the following order: THP-1 = U937 > HL-60 > BALL-1 = MOLT-4. In THP-1 cells, beta-toxin formed oligomers on lipid rafts in membranes and induced the efflux of K(+) from THP-1 cells in a dose- and time-dependent manner. The phosphorylation of p38 MAPK and JNK occurred in response to an attack by beta-toxin. p38 MAPK (SB203580) and JNK (SP600125) inhibitors enhanced toxin-induced cell death. Incubation in K(+)-free medium intensified p38 MAPK activation and cell death induced by the toxin, while incubation in K(+)-high medium prevented those effects. While streptolysin O (SLO) reportedly activates p38 MAPK via reactive oxygen species (ROS), we showed that this pathway did not play a major role in p38 phosphorylation in beta-toxin-treated cells. Therefore, we propose that beta-toxin induces activation of the MAPK pathway to promote host cell survival.
|
| 巻・号 |
81(10)
|
| ページ |
3703-8
|
| 公開日 |
2013-10-1
|
| DOI |
10.1128/IAI.00579-13
|
| PII |
IAI.00579-13
|
| PMID |
23876806
|
| PMC |
PMC3811753
|
| MeSH |
Bacterial Toxins / metabolism
Bacterial Toxins / toxicity*
Cell Line, Tumor
Cell Survival
Clostridium perfringens / metabolism*
Gene Expression Regulation, Enzymologic / drug effects*
Humans
JNK Mitogen-Activated Protein Kinases / genetics
JNK Mitogen-Activated Protein Kinases / metabolism*
p38 Mitogen-Activated Protein Kinases / genetics
p38 Mitogen-Activated Protein Kinases / metabolism*
|
| IF |
3.201
|
| 引用数 |
24
|
|
WOS 分野
|
INFECTIOUS DISEASES
IMMUNOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
THP-1(RCB1189)
HL60(RCB0041)
MOLT-4(RCB0206)
BALL-1 |
