title: 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.
abstract: 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)-1β and IL-6, and chemokines IL-8 and macrophage inflammatory protein (MIP)-1β, 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-1β, IL-6, and MIP-1β(3 after 2 h stimulation, the synergism in the up-regulation of IL-1β and IL-6 mRNA was observed after 8-h and 24-h stimulation, respectively, whereas there was no synergistic effect on MIP-1β. Our results demonstrate that CpG-ODN synergizes with poly I:C to induce pro-inflammatory immune response in chicken monocytes.
authors.affiliation: Southern Plains Agricultural Research Center, Agricultural Research Service, U.S. Department of Agriculture, College Station, Texas, USA. haiqi.he@ars.usda.gov
authors.forename: Haiqi
authors.initials: H
authors.lastname: He
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: MacKinnon
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Genovese
authors.forename: Michael H
authors.initials: MH
authors.lastname: Kogut
mesh_terms: D000818:Animals; D030161:Avian Proteins / Q000819:agonists; D002478:Cells, Cultured; D002645:Chickens; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004357:Drug Synergism; D018836:Inflammation Mediators / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D011070:Poly I-C / Q000494:pharmacology; D012330:RNA, Double-Stranded / Q000494:pharmacology*; D020239:Receptor Cross-Talk; D051193:Toll-Like Receptors / Q000819:agonists
chemical_list: D030161:Avian Proteins; C408982:CPG-oligonucleotide; D016207:Cytokines; D018836:Inflammation Mediators; D009838:Oligodeoxyribonucleotides; D012330:RNA, Double-Stranded; D051193:Toll-Like Receptors; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D011070:Poly I-C