Division of Molecular Medicine, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Virol J. 2013 Apr 4;10:105. doi: 10.1186/1743-422X-10-105.
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.
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.
DENV induces CD137 signaling to enhance apoptosis by increasing TNF-α production via activation of p38 MAPK.
登革热病毒（DENV）感染导致的肝损伤可通过肝肿大和转氨酶水平升高得到证实。DENV 在肝细胞内复制，并在体外和体内引起肝细胞凋亡。了解 DENV 诱导肝损伤的分子机制可以促进替代化学治疗药物和改进治疗方法的开发。
p38 丝裂原活化蛋白激酶（MAPK）参与凋亡相关信号转导和促炎细胞因子的产生。使用 RNA 干扰技术研究了 p38 MAPK 在 DENV 感染的 HepG2 细胞中的作用。结果表明，DENV 感染激活了 p38 MAPK 并诱导了细胞凋亡。p38 MAPK 和 CD137 信号通路控制着 DENV 感染的 HepG2 细胞中 p38 MAPK 的激活和 TNF-α 的产生，因为在 p38 MAPK 和 CD137 耗尽的 DENV 感染的 HepG2 细胞中，p38 MAPK 的激活、TNF-α 和凋亡明显减少。将外源性 TNF-α添加到 p38 MAPK 耗尽的 DENV 感染的 HepG2 细胞中，可恢复 DENV 诱导的 HepG2 细胞凋亡。
DENV 通过激活 p38 MAPK 增加 TNF-α 的产生来诱导 CD137 信号，从而增强细胞凋亡。
