title: IRF3 and ERK MAP-kinases control nitric oxide production from macrophages in response to poly-I:C.
abstract: Understanding nitric oxide (NO) in innate anti-viral immunity and immune-mediated pathology is hampered by incomplete details of its transcriptional and signaling factors. We found in macrophages that IRF3, ERK MAP-kinases, and PKR are essential to NO production in response to RNA-virus mimic, poly I:C, a TLR3 agonist. ERK's role in NO induction may be through phosphorylation of serine-171 of IRF3 and expression of NO-inducing cytokines, IL-6 and IFN-β. However, these cytokines induced less NO in IRF3 knockout or knockdown macrophages. These findings show that ERK and IRF3 coordinate induction of NO by macrophages in response to stimulation of TLR3.
authors.affiliation: School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, NE, USA.
authors.forename: Tyler C
authors.initials: TC
authors.lastname: Moore
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Petro
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D050838:Interferon Regulatory Factor-3 / Q000172:deficiency / Q000235:genetics*; D016899:Interferon-beta / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009569:Nitric Oxide / Q000096:biosynthesis; D011070:Poly I-C / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D015398:Signal Transduction
chemical_list: D050838:Interferon Regulatory Factor-3; D015850:Interleukin-6; C494233:Irf3 protein, mouse; D008070:Lipopolysaccharides; D047428:Protein Kinase Inhibitors; D009569:Nitric Oxide; D016899:Interferon-beta; D048049:Extracellular Signal-Regulated MAP Kinases; D011070:Poly I-C
keywords: BL/6; C57BL/6 mice; ERK; ERK MAP-kinase; IRF3; IRF3 deficient mice; IRF3KO; Interferon response factor-3; Interleukin-6; LPS; Macrophages; NF-κB; NO; Nitric oxide; ODN; PI3K; PKR; Poly I:C; TIR; TIR domain-containing adaptor-inducing IFN-β; TLR; TRIF; extracellular signal related kinase; interferon response factor 3; lipopolysaccharide; nitric oxide; nuclear factor κ-B; oligodeoxynucleotide; phosphoinositide-3-kinase; protein kinase R; toll like receptor; toll/IL-1 receptor
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