Dengue Virus Infection Causes the Activation of Distinct NF- κ B Pathways for Inducible Nitric Oxide Synthase and TNF- Expression in RAW264.7 Cells

Yi-Lin Cheng, Yee-Shin Lin, Chia-Ling Chen, Shu-Wen Wan, Yi-Dan Ou, Chia-Yi Yu, Tsung-Ting Tsai, Po-Chun Tseng, Chiou Feng Lin

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Infection with dengue virus (DENV) causes an increase in proinflammatory responses, such as nitric oxide (NO) generation and TNF-expression; however, the molecular mechanism underlying this inflammatory activation remains undefined, although the activation of the transcription factor NF-B is generally involved. In addition to TNF- production in DENV-infected murine macrophage RAW264.7 cells, inducible NO synthase was transcriptionally and posttranslationally elevated and accompanied by NO generation. NF-B is known to be activated by DENV infection. Pharmacologically inhibiting NF-B activation abolishes iNOS/NO biosynthesis and TNF- production. With inhibition, the potential role of NF-B in oxidative signaling regulation was prevented during DENV infection. Heat-inactivated DENV failed to cause the identified inflammatory responses. Pharmacological inhibition of TLR3 partly decreased NF-B activation; however, it effectively abolished inducible iNOS/NO biosynthesis but did not inhibit TNF- production. In contrast to TLR3, viral protein NS2B3 also independently contributed to NF-B activation to regulate TNF- production. These results show the distinct pathways for NF-B activation caused by DENV infection individually for the regulation of iNOS/NO and TNF- expression.

Original languageEnglish
Article number274025
JournalMediators of Inflammation
Publication statusPublished - 2015


ASJC Scopus subject areas

  • Immunology
  • Cell Biology

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