title: Poly I:C enhances production of nitric oxide in response to interferon-γ via upregulation of interferon regulatory factor 7 in vascular endothelial cells.
abstract: The effect of poly I:C on interferon (IFN)-γ-induced nitric oxide (NO) production in vascular endothelial cells was examined using murine aortic endothelial END-D cells. Poly I:C augmented IFN-γ-induced NO production although it alone did not induce the NO production. Poly I:C augmented the NO production via enhanced expression of an inducible NO synthase protein. Poly I:C did not affect the activation of Janus kinase (JAK) 1/2, and signal transducer and activator of transcription (STAT) 1 in IFN-γ signaling. Moreover, there was no significant difference in the IFN-γ-induced interferon regulatory factor (IRF) 1 expression between the presence and absence of poly I:C. Poly I:C led to the activation of IRF7 in END-D cells. Inhibition of poly I:C signaling by amlexanox, an inhibitor of TANK-binding kinase (TBK) 1 and IκB kinase (IKK) ε, abolished the augmentation of IFN-γ-induced NO production. Therefore, poly I:C was suggested to augment IFN-γ-induced NO production at the transcriptional level via enhanced IRF7 activation.
authors.affiliation: Department of Surgery, Aichi Medical University School of Medicine, Nagakute, Aichi 480-1195, Japan.
authors.forename: Daiki
authors.initials: D
authors.lastname: Mori
authors.affiliation: Department of Microbiology and Immunology, Aichi Medical University School of Medicine, Nagakute, Aichi 480-1195, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Koide
authors.affiliation: Department of Microbiology and Immunology, Aichi Medical University School of Medicine, Nagakute, Aichi 480-1195, Japan.
authors.forename: Bilegtsaikhan
authors.initials: B
authors.lastname: Tsolmongyn
authors.affiliation: Department of Surgery, Aichi Medical University School of Medicine, Nagakute, Aichi 480-1195, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nagata
authors.affiliation: Department of Surgery, Aichi Medical University School of Medicine, Nagakute, Aichi 480-1195, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Sano
authors.affiliation: Department of Surgery, Aichi Medical University School of Medicine, Nagakute, Aichi 480-1195, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Nonami
authors.affiliation: Department of Microbiology and Immunology, Aichi Medical University School of Medicine, Nagakute, Aichi 480-1195, Japan. Electronic address: yokochi@aichi-med-u.ac.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yokochi
mesh_terms: D000631:Aminopyridines / Q000737:chemistry; D000818:Animals; D001011:Aorta / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000166:cytology*; D004791:Enzyme Inhibitors / Q000737:chemistry; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism; D050839:Interferon Regulatory Factor-7 / Q000378:metabolism*; D007371:Interferon-gamma / Q000494:pharmacology*; D051379:Mice; D009569:Nitric Oxide / Q000737:chemistry*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D009573:Nitrites / Q000737:chemistry; D010766:Phosphorylation; D011070:Poly I-C / Q000737:chemistry*; D015398:Signal Transduction
chemical_list: D000631:Aminopyridines; D004791:Enzyme Inhibitors; D050838:Interferon Regulatory Factor-3; D050839:Interferon Regulatory Factor-7; C494233:Irf3 protein, mouse; C494235:Irf7 protein, mouse; D009573:Nitrites; D009569:Nitric Oxide; D007371:Interferon-gamma; C045742:amlexanox; D019001:Nitric Oxide Synthase; D011070:Poly I-C
keywords: IFN-γ; IRF7; Nitric oxide (NO); Poly I:C; Vascular endothelial cells