title: Interferon-alpha/beta receptor-mediated selective induction of a gene cluster by CpG oligodeoxynucleotide 2006.
abstract: BACKGROUND
  Oligodeoxynucleotides containing unmethylated CpG motifs (CpG ODN) are known to exert a strong adjuvant effect on Th1 immune responses. Although several genes have been reported, no comprehensive study of the gene expression profiles in human cells after stimulation with CpG ODN has been reported.
  
  
  RESULTS
  This study was designed to identify a CpG-inducible gene cluster that potentially predicts for the molecular mechanisms of clinical efficacy of CpG ODN, by determining mRNA expression in human PBMC after stimulation with CpG ODN. PBMCs were obtained from the peripheral blood of healthy volunteers and cultured in the presence or absence of CpG ODN 2006 for up to 24 hours. The mRNA expression profile was evaluated using a high-density oligonucleotide probe array, GeneChip. Using hierarchical clustering-analysis, out of a total of 10,000 genes we identified a cluster containing 77 genes as having been up-regulated by CpG ODN. This cluster was further divided into two sub-clusters by means of time-kinetics. (1) Inflammatory cytokines such as IL-6 and GM-CSF were up-regulated predominantly 3 to 6 hours after stimulation with CpG ODN, presumably through activation of a transcription factor, NF-kappaB. (2) Interferon (IFN)-inducible anti-viral proteins, including IFIT1, OAS1 and Mx1, and Th1 chemoattractant IP-10, were up-regulated predominantly 6 to 24 hours after stimulation. Blocking with mAb against IFN-alpha/beta receptor strongly inhibited the induction of these IFN-inducible genes by CpG ODN.
  
  
  CONCLUSIONS
  This study provides new information regarding the possible immunomodulatory effects of CpG ODN in vivo via an IFN-alpha/beta receptor-mediated paracrine pathway.
authors.affiliation: Department of Allergy & Immunology, National Research Institute for Child Health & Development, Tokyo, Japan. atkato@nch.go.jp
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kato
authors.forename: Toshiki
authors.initials: T
authors.lastname: Homma
authors.forename: Jonathan
authors.initials: J
authors.lastname: Batchelor
authors.forename: Noriko
authors.initials: N
authors.lastname: Hashimoto
authors.forename: Shosuke
authors.initials: S
authors.lastname: Imai
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Wakiguchi
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Saito
authors.forename: Kenji
authors.initials: K
authors.lastname: Matsumoto
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000998:Antiviral Agents / Q000235:genetics; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics; D004247:DNA / Q000276:immunology* / Q000494:pharmacology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008565:Membrane Proteins; D005810:Multigene Family / Q000276:immunology*; D009838:Oligodeoxyribonucleotides / Q000276:immunology* / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon / Q000187:drug effects / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D000911:Antibodies, Monoclonal; D000998:Antiviral Agents; D016207:Cytokines; D007370:Interferon Type I; D008565:Membrane Proteins; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D017471:Receptors, Interferon; D053633:Receptor, Interferon alpha-beta; D004247:DNA