Publication: JNK1/2 inhibitor reduces dengue virus-induced liver injury
Issued Date
2017-05-01
Resource Type
ISSN
18729096
01663542
01663542
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2-s2.0-85012110613
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Mahidol University
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SCOPUS
Bibliographic Citation
Antiviral Research. Vol.141, (2017), 7-18
Suggested Citation
Gopinathan Pillai Sreekanth, Aporn Chuncharunee, Boonyarit Cheunsuchon, Sansanee Noisakran, Pa thai Yenchitsomanus, Thawornchai Limjindaporn JNK1/2 inhibitor reduces dengue virus-induced liver injury. Antiviral Research. Vol.141, (2017), 7-18. doi:10.1016/j.antiviral.2017.02.003 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/42844
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Title
JNK1/2 inhibitor reduces dengue virus-induced liver injury
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Abstract
© 2017 Elsevier B.V. High viral load with liver injury is exhibited in severe dengue virus (DENV) infection. Mitogen activated protein kinases (MAPKs) including ERK1/2 and p38 MAPK were previously found to be involved in the animal models of DENV-induced liver injury. However, the role of JNK1/2 signaling in DENV-induced liver injury has never been investigated. JNK1/2 inhibitor, SP600125, was used to investigate the role of JNK1/2 signaling in the BALB/c mouse model of DENV-induced liver injury. SP600125-treated DENV-infected mice ameliorated leucopenia, thrombocytopenia, hemoconcentration, liver transaminases and liver histopathology. DENV-induced liver injury exhibited induced phosphorylation of JNK1/2, whereas SP600125 reduced this phosphorylation. An apoptotic real-time PCR array profiler was used to screen how SP600125 affects the expression of 84 cell death-associated genes to minimize DENV-induced liver injury. Modulation of caspase-3, caspase-8 and caspase-9 expressions by SP600125 in DENV-infected mice suggests its efficiency in restricting apoptosis via both extrinsic and intrinsic pathways. Reduced expressions of TNF-α and TRAIL are suggestive to modulate the extrinsic apoptotic signals, where reduced p53 phosphorylation and induced anti-apoptotic Bcl-2 expression indicate the involvement of the intrinsic apoptotic pathway. This study thus demonstrates the pivotal role of JNK1/2 signaling in DENV-induced liver injury and how SP600125 modulates this pathogenesis.