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Inhibition of p38MAPK and CD137 signaling reduce dengue virus-induced TNF-alpha secretion and apoptosis
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Document Title
Inhibition of p38MAPK and CD137 signaling reduce dengue virus-induced TNF-alpha secretion and apoptosis
Author
Nagila A, Netsawang J, Suttitheptumrong A, Morchang A, Khunchai S, Srisawat C, Puttikhunt C, Noisakran S, Yenchitsomanus PT, Limjindaporn T
Name from Authors Collection
Affiliations
Mahidol University; Mahidol University; Mahidol University; Mahidol University; Rangsit University; National Science & Technology Development Agency - Thailand; National Center Genetic Engineering & Biotechnology (BIOTEC)
Type
Article
Source Title
VIROLOGY JOURNAL
ISSN
1743-422X
Year
2013
Volume
10
Page
-
Open Access
gold, Green Published
Publisher
BIOMED CENTRAL LTD
DOI
10.1186/1743-422X-10-105
Format
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-alpha production were controlled by p38 MAPK and CD137 signaling in DENV-infected HepG2 cells as activated p38 MAPK, TNF-alpha and apoptosis were significantly decreased in p38 MAPK and CD137 depleted DENV-infected HepG2 cells. Addition of exogenous TNF-alpha 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-a production via activation of p38 MAPK.
Keyword
Apoptosis | CD137 | Dengue virus | p38MAPK | TNF-alpha
Industrial Classification
Knowledge Taxonomy Level 1
Knowledge Taxonomy Level 2
Funding Sponsor
Mahidol University; Siriraj Research Developmental Fund; TRF-Royal Golden Jubilee (TRF-RGJ) Ph.D. Program; CHE under the program strategic scholarship for frontier research network for the join Ph.D. program; Siriraj Developmental Scholarship; Siriraj Graduate Thesis Scholarship
License
CC BY
Rights
Nagila et al.; licensee BioMed Central Ltd
Publication Source
WOS