Immunostimulation and anti-DNA antibody production by backbone modified CpG-DNA

被引：31

作者：

Kim, Dongbum ^{[1
,2
]}

Rhee, Jae Won ^{[1
]}

Kwon, Sanghoon ^{[2
]}

Sohn, Wern-Joo ^{[1
]}

Lee, Younghee ^{[3
]}

Kim, Dae-Won ^{[4
]}

Kim, Doo-Sik ^{[4
]}

Kwon, Hyung-Joo ^{[1
,2
]}

机构：

[1] Hallym Univ, Coll Med, Ctr Med Sci Res, Gangwon Do 200702, South Korea

[2] Hallym Univ, Coll Med, Dept Microbiol, Gangwon Do 200702, South Korea

[3] Chungbuk Natl Univ, Coll Nat Sci, Dept Biochem, Chungbuk 361763, South Korea

[4] Yonsei Univ, Coll Sci, Dept Biochem, Seoul 120749, South Korea

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2009年 / 379卷 / 02期

关键词：

CpG-DNA; Igm; Phosphorothioate modification; TLR; TOLL-LIKE RECEPTORS; B-CELL ACTIVATION; NF-KAPPA-B; BACTERIAL-DNA; PHOSPHOROTHIOATE OLIGODEOXYNUCLEOTIDES; TOLL-LIKE-RECEPTOR-9; ACTIVATION; IMMUNE STIMULATION; GENE-EXPRESSION; RAW-264.7; CELLS; MOTIFS;

D O I：

10.1016/j.bbrc.2008.12.063

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Oligodeoxynucleotides containing immunostimulatory CpG motifs (CpG-DNA) have gained attention as potentially useful therapeutics. However, the phosphorothioate-modified CpG-DNAs (PS-ODN) can induce backbone-related side effects. Here, we compared the immunostimulatory activity of natural phosphodiester CpG-DNA (PO-ODN) from Mycobacterium bovis and PS-ODN in mice. Both PO-ODN and PS-ODN induced production of IL-12. PS-ODN increased spleen weights, spleen cell numbers, and the migration of macrophages into the peritoneal cavity in the mice in a CG sequence-dependent manner. PS-ODN induced anti-PS-ODN antibody production in the mice, and the PS-ODN-specific IgM was cross-reactive with other PS-ODNs in a CG sequence-independent manner. In contrast, PO-ODN did not affect on spleen weights, cell numbers. or IgM production. These results may provide an explanation for the side effects in immunotherapeutic application of PS-ODN. They also suggest that PO-ODN may be more optimal than PS-ODN to enhance innate immune responses without severe side effects. (c) 2008 Elsevier Inc. All rights reserved.

引用

页码：362 / 367

页数：6

共 33 条

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