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Acta Pharmacologica Sinica
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Structure-efficacy relationships of immunostimulatory activity of CpG-containing oligodeoxynucleotides on mouse spleen cells
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  • Original Article
  • Published: 01 October 2007

Immunopharmacology

Structure-efficacy relationships of immunostimulatory activity of CpG-containing oligodeoxynucleotides on mouse spleen cells

  • Hai-yan Du2,
  • Shao-you Xia3,
  • Hai-feng Song1,
  • Na Li1,
  • Ming-mei Shang1,
  • Jia Zou1,
  • Qing-qing Wang1,
  • Lun Ou1,
  • Xiao Sun1,
  • Ai-guo Ji2 &
  • …
  • Zhong-ming Tang1 

Acta Pharmacologica Sinica volume 28, pages 1637–1644 (2007)Cite this article

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Abstract

Aim:

To study the relationship between primary structures of oligodeoxynucleo-tides (ODN) containing unmethylated deoxycytidyl-deoxyguanosine (CpG) dinucleotide motifs and their immunostimulatory activities in mouse spleen cells.

Methods:

A series of CpG ODN with different primary structures were synthesized. Their capabilities to stimulate mouse spleen cell proliferation were determined by [3H]thymidine incorporation assay. Cytokine (interleukin [IL]-6, IL-12, and IFN-α) secretion spectra induced by CpG ODN were assessed by ELISA. The ability of CpG ODN to activate natural killer cells was evaluated by standard 4 h 51Cr-release assay. Flow cytometry was utilized to examine the expressions of various lymphocyte surface molecules on diverse immunocytes. An effective CpG ODN for murine, ODN1826, was set as the template of modification and the positive control.

Results:

The immunostimulatory activities of CpG ODN with different sequences and compositions varied markedly, both in character and in extent. It was useless for improving the immunostimulatory activity of ODN1826 by simply increasing the functional hexameric CpG motif number, modifying the site of CpG motifs, or changing the distance between multi-CpG motifs. However, an addition of a self-complementary palindrome structure at the 3′-end, but not the 5′-end of CpG ODN, aroused marked improvement in its activity. Several designed ODN had superior comprehensive immunostimulatory properties compared to ODN1826.

Conclusion:

The immunostimulatory activity of a CpG ODN was relevant to its primary structure. It was useless for promoting immunostimulatory activity to simply change CpG motif number, space, or distance. The 3′-end palindrome structure of CpG ODN is associated with enhanced immunostimulatory activity.

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Author information

Authors and Affiliations

  1. Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing, 100850, China

    Hai-feng Song, Na Li, Ming-mei Shang, Jia Zou, Qing-qing Wang, Lun Ou, Xiao Sun & Zhong-ming Tang

  2. Institute of Biochemical and Biotech Drugs, School of Pharmacy, Shandong University, Ji-nan, 250012, China

    Hai-yan Du & Ai-guo Ji

  3. Department of General Surgery, General Hospital of PLA, Beijing, 100853, China

    Shao-you Xia

Authors
  1. Hai-yan Du
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  2. Shao-you Xia
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  3. Hai-feng Song
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  6. Jia Zou
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Corresponding author

Correspondence to Hai-feng Song.

Additional information

Project supported by grants from the National Natural Science Foundation of China (No 30500625) and the National High Biotechnology Development Program of China (No 2003AA2Z347B).

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Cite this article

Du, Hy., Xia, Sy., Song, Hf. et al. Structure-efficacy relationships of immunostimulatory activity of CpG-containing oligodeoxynucleotides on mouse spleen cells. Acta Pharmacol Sin 28, 1637–1644 (2007). https://doi.org/10.1111/j.1745-7254.2007.00628.x

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  • Received: 17 February 2007

  • Accepted: 19 April 2007

  • Issue date: 01 October 2007

  • DOI: https://doi.org/10.1111/j.1745-7254.2007.00628.x

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Keywords

  • CpG
  • oligodeoxynucleotides
  • immuno-stimulation
  • structure-activity relationship

This article is cited by

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ISSN 1745-7254 (online)

ISSN 1671-4083 (print)

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