CG sequence- and phosphorothioate backbone modification-dependent activation of the NF-kappaB-responsive gene

Keun-Wook Lee1, Doo-Sik Kim, Hyung-Joo Kwon

  • 1Department of Biochemistry, College of Science, Yonsei University, Seoul 120-749, South Korea.

Molecular Immunology
|August 11, 2004
PubMed

Insights

CpG-ODNs activate immune cells. Phosphorothioate-modified CpG-ODN 1826 stimulates human B cells, activating NF-kappaB and inflammatory gene expression, similar to its effect on mouse cells.

Area of Science:

  • Immunology
  • Molecular Biology

Background:

  • Oligodeoxynucleotides with CpG motifs (CpG-ODNs) are known to stimulate innate immune responses.
  • CpG-ODN 1826 is effective in mouse cells, while CpG-ODN 2006 is optimal for human cells.

Purpose of the Study:

  • To investigate the activation of IL-8 promoter and NF-kappaB in human B cells by CpG-ODN 1826 and 2006.
  • To determine the role of CG sequence and phosphorothioate backbone modification in CpG-ODN activity.
  • To identify signaling molecules involved in CpG-ODN triggered pathways.

Main Methods:

  • Stimulation of human B cell line RPMI 8226 with CpG-ODN 1826 and 2006.
  • Analysis of IL-8 promoter activation and NF-kappaB nuclear localization.
  • Investigating the involvement of myeloid differentiation protein and tumor necrosis factor receptor-associated factor 6.

Main Results:

  • CpG-ODN 1826 and 2006 activated the IL-8 promoter and NF-kappaB in human B cells in a sequence- and backbone-dependent manner.
  • Myeloid differentiation protein and TRAF6 were implicated in the CpG-ODN signaling pathway.
  • Phosphorothioate-modified CpG-ODN 1826 induced NF-kappaB-responsive inflammatory cytokine gene expression in human B cells.

Conclusions:

  • Phosphorothioate-modified CpG-ODN 1826 activates human B cells, inducing NF-kappaB-responsive gene expression.
  • CpG-ODN 1826 demonstrates cross-species activity, stimulating both mouse and human immune cells.

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