Inhibition of p38MAPK and CD137 signaling reduce dengue virus-induced TNF-α secretion and apoptosis.
Virol J
; 10: 105, 2013 Apr 04.
Article
in En
| MEDLINE
| ID: mdl-23557259
ABSTRACT
BACKGROUND:
Hepatic injury in dengue virus (DENV) infection is authenticated by hepatomegaly and an upsurge in transaminase levels. DENV replicates in hepatocytes and causes hepatocyte apoptosis both in vitro and in vivo. Understanding the molecular mechanisms of DENV-induced hepatic injury could facilitate the development of alternate chemotherapeutic agents and improved therapies.FINDINGS:
The p38 mitogen-activated protein kinase (MAPK) participates in both apoptosis-related signaling and pro- inflammatory cytokine production. The role of p38 MAPK in DENV-infected HepG2 cells was examined using RNA interference. The results showed that DENV infection activated p38 MAPK and induced apoptosis. The p38 MAPK activation and TNF-α production were controlled by p38 MAPK and CD137 signaling in DENV-infected HepG2 cells as activated p38 MAPK, TNF-α and apoptosis were significantly decreased in p38 MAPK and CD137 depleted DENV-infected HepG2 cells. Addition of exogenous TNF-α to p38 MAPK depleted DENV-infected HepG2 cells restored DENV-induced apoptosis in HepG2 cells.CONCLUSION:
DENV induces CD137 signaling to enhance apoptosis by increasing TNF-α production via activation of p38 MAPK.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Signal Transduction
/
Tumor Necrosis Factor-alpha
/
Apoptosis
/
Dengue Virus
/
P38 Mitogen-Activated Protein Kinases
/
Tumor Necrosis Factor Receptor Superfamily, Member 9
Limits:
Humans
Language:
En
Journal:
Virol J
Journal subject:
VIROLOGIA
Year:
2013
Document type:
Article
Affiliation country:
Thailand
Publication country:
ENGLAND
/
ESCOCIA
/
GB
/
GREAT BRITAIN
/
INGLATERRA
/
REINO UNIDO
/
SCOTLAND
/
UK
/
UNITED KINGDOM