RGD Reference Report - JNK1/2 inhibitor reduces dengue virus-induced liver injury. - Rat Genome Database

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JNK1/2 inhibitor reduces dengue virus-induced liver injury.

Authors: Sreekanth, Gopinathan Pillai  Chuncharunee, Aporn  Cheunsuchon, Boonyarit  Noisakran, Sansanee  Yenchitsomanus, Pa-Thai  Limjindaporn, Thawornchai 
Citation: Sreekanth GP, etal., Antiviral Res. 2017 May;141:7-18. doi: 10.1016/j.antiviral.2017.02.003. Epub 2017 Feb 7.
RGD ID: 150340680
Pubmed: (View Article at PubMed) PMID:28188818
DOI: Full-text: DOI:10.1016/j.antiviral.2017.02.003

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┬ácell 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.

Annotation

Disease Annotations    
dengue disease  (IEP,ISO)

Objects Annotated

Genes (Rattus norvegicus)
Mapk8  (mitogen-activated protein kinase 8)

Genes (Mus musculus)
Mapk8  (mitogen-activated protein kinase 8)

Genes (Homo sapiens)
MAPK8  (mitogen-activated protein kinase 8)


Additional Information