Email updates

Keep up to date with the latest news and content from Virology Journal and BioMed Central.

Open Access Short report

Inhibition of p38MAPK and CD137 signaling reduce dengue virus-induced TNF-α secretion and apoptosis

Amar Nagila12, Janjuree Netsawang5, Aroonroong Suttitheptumrong14, Atthapan Morchang14, Sasiprapa Khunchai14, Chatchawan Srisawat, Chunya Puttikhunt6, Sansanee Noisakran6, Pa-thai Yenchitsomanus1 and Thawornchai Limjindaporn13*

Author Affiliations

1 Division of Molecular Medicine, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand

2 Department of Biochemistry, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand

3 Department of Anatomy, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand

4 Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand

5 Faculty of Medical Technology, Rangsit University, Bangkok, Thailand

6 Medical Biotechnology Research Unit, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Bangkok, Thailand

For all author emails, please log on.

Virology Journal 2013, 10:105  doi:10.1186/1743-422X-10-105

Published: 4 April 2013

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.

Keywords:
Dengue virus; Apoptosis; TNF-α; p38MAPK; CD137