Interferon-α/β receptor-mediated selective induction of a gene cluster by CpG oligodeoxynucleotide 2006

doi:10.1186/1471-2172-4-8

BMC Immunology
Volume 4

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Kato A
Homma T
Batchelor J
Hashimoto N
Imai S
Wakiguchi H
Saito H
Matsumoto K

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Kato A
Homma T
Batchelor J
Hashimoto N
Imai S
Wakiguchi H
Saito H
Matsumoto K
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Research article

Interferon-α/β receptor-mediated selective induction of a gene cluster by CpG oligodeoxynucleotide 2006

Atsushi Kato¹^,2 , Toshiki Homma¹^,2 , Jonathan Batchelor³ , Noriko Hashimoto¹ , Shosuke Imai⁴ , Hiroshi Wakiguchi⁵ , Hirohisa Saito¹^,6 and Kenji Matsumoto¹^,6

¹Department of Allergy & Immunology, National Research Institute for Child Health & Development, Tokyo, Japan

²Genox Research, Inc., Kawasaki, Japan

³Division of Allergy, National Center for Child Health and Development, Tokyo, Japan

⁴Department of Microbiology, Kochi Medical School, Kochi, Japan

⁵Department of Pediatrics, Kochi Medical School, Kochi, Japan

⁶Research Team for Allergy Transcriptome, RIKEN Research Center for Allergy & Immunology, Yokohama, Japan

author email corresponding author email

BMC Immunology 2003, 4:8doi:10.1186/1471-2172-4-8


Published:	30 July 2003

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-κB. (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-α/β receptor strongly inhibited the induction of these IFN-inducible genes by CpG ODN.

Conclusion

This study provides new information regarding the possible immunomodulatory effects of CpG ODN in vivo via an IFN-α/β receptor-mediated paracrine pathway.