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.
|Journal||Mediators of Inflammation|
|Publication status||Published - 2015|
ASJC Scopus subject areas
- Cell Biology