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

Abstract

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

• Authors: 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
• Journal: Mediators of inflammation (Mediators Inflamm) Vol. 2015 Pg. 274025 ( 2015) ISSN: 1466-1861 [Electronic] United States
• PMID: 26199460 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Caffeic Acids
• NF-kappa B
• Tumor Necrosis Factor-alpha
• Nitric Oxide
• Nitric Oxide Synthase Type II
• caffeic acid phenethyl ester
• Phenylethyl Alcohol

Topics

• Animals
• Caffeic Acids (pharmacology)
• Cell Line
• Dengue Virus (pathogenicity)
• Macrophages (drug effects, metabolism, virology)
• Mice
• NF-kappa B (physiology)
• Nitric Oxide (metabolism)
• Nitric Oxide Synthase Type II (metabolism)
• Phenylethyl Alcohol (analogs & derivatives, pharmacology)
• Signal Transduction (drug effects)
• Tumor Necrosis Factor-alpha (metabolism)