title: 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.affiliation: Institute of Basic Medical Science, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.
authors.forename: Yi-Lin
authors.initials: YL
authors.lastname: Cheng
authors.affiliation: Institute of Basic Medical Science, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan ; Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan ; Center of Infectious Diseases and Signaling Research, National Cheng Kung University, Tainan 701, Taiwan.
authors.forename: Yee-Shin
authors.initials: YS
authors.lastname: Lin
authors.affiliation: Translational Research Center, Taipei Medical University, Taipei 110, Taiwan.
authors.forename: Chia-Ling
authors.initials: CL
authors.lastname: Chen
authors.affiliation: Center of Infectious Diseases and Signaling Research, National Cheng Kung University, Tainan 701, Taiwan.
authors.forename: Shu-Wen
authors.initials: SW
authors.lastname: Wan
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.
authors.forename: Yi-Dan
authors.initials: YD
authors.lastname: Ou
authors.affiliation: Center of Infectious Diseases and Signaling Research, National Cheng Kung University, Tainan 701, Taiwan.
authors.forename: Chia-Yi
authors.initials: CY
authors.lastname: Yu
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.
authors.forename: Tsung-Ting
authors.initials: TT
authors.lastname: Tsai
authors.affiliation: Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.
authors.forename: Po-Chun
authors.initials: PC
authors.lastname: Tseng
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, Taipei Medical University, Taipei 110, Taiwan ; Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.
authors.forename: Chiou-Feng
authors.initials: CF
authors.lastname: Lin
mesh_terms: D000818:Animals; D002109:Caffeic Acids / Q000494:pharmacology; D002460:Cell Line; D003716:Dengue Virus / Q000472:pathogenicity*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism* / Q000821:virology*; D051379:Mice; D016328:NF-kappa B / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D002109:Caffeic Acids; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol