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CpG oligodeoxynucleotide and double-stranded RNA synergize to enhance nitric oxide production and mRNA expression of inducible nitric oxide synthase, pro-inflammatory cytokines, and chemokines in chicken monocytes

He, Haiqi, MacKinnon, Kathryn M., Genovese, Kenneth J., Kogut, Michael H.
Journal of Innate Immunity 2010 v.17 no.2 pp. 137
chemokines, chickens, double-stranded RNA, gene expression, gene expression regulation, immune response, inflammation, messenger RNA, monocytes, nitric oxide, nitric oxide synthase, oligodeoxyribonucleotides, synergism
Toll-like receptors (TLRs) recognize microbial components and initiate the innate immune responses that control microbial infections. The interaction between ligands of TLR3 and TLR9, poly I:C (an analog of viral double-stranded RNA) and CpG-ODN (a CpG-motif containing oligodeoxydinucleotide) on the inflammatory immune responses, including the production of nitric oxide (NO) and the expression of inducible NO synthase (iNOS), pro-inflammatory cytokines interleukin (IL)-1b and IL-6, and chemokines IL-8 and macrophage inflammatory protein (MIP)-1b, were investigated in chicken monocytes. The NO production was significantly higher when stimulated with a combination of CpG-ODN and poly I:C than with either CpG-ODN or poly I:C alone. Similarly, a significant synergistic effect by CpG-ODN and poly I:C was observed in the up-regulation of iNOS and IL-8 mRNA after 2 h and persisted up to 24 h. Although the combinatory treatment of CpG-ODN and poly I:C enhanced the expression of IL-1b, IL-6, and MIP-1b after 2 h stimulation, the synergism in the up-regulation of IL-1b and IL-6 mRNA was observed after 8-h and 24-h stimulation, respectively, whereas there was no synergistic effect on MIP-1b. Our results demonstrate that CpG-ODN synergizes with poly I:C to induce pro-inflammatory immune response in chicken monocytes.