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.
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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