Regulation of CpG-induced immune activation by suppressive oligodeoxynucleotides

被引：29

作者：

Klinman, DM ^{[1
]}

Zeuner, R ^{[1
]}

Yamada, H ^{[1
]}

Gursel, M ^{[1
]}

Currie, D ^{[1
]}

Gursel, I ^{[1
]}

机构：

[1] US FDA, Ctr Biol Evaluat & Res, Sect Retroviral Res, Bethesda, MD 20892 USA

来源：

THERAPEUTIC OLIGONUCLEOTIDES: ANTISENSE, RNAI, TRIPLE-HELIX, GENE REPAIR, ENHANCER DECOYS, CPG AND DNA CHIPS | 2003年 / 1002卷

关键词：

synthetic oligonucleotides; CpG motifs; immune activation;

D O I：

10.1196/annals.1281.023

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

Bacterial DNA and synthetic oligodeoxynucleotides (ODN) containing unmethylated "CpG motifs" stimulate an innate immune response characterized by the production of cytokines, chemokines, and polyreactive Igs that promote host survival following infectious challenge. Yet CpG-driven immune activation can have deleterious consequences, such as increasing the host's susceptibility to autoimmune disease. The immunomodulatory activity of CpG DNA can be blocked by DNA containing "suppressive" motifs. This work explores the rules governing cellular recognition of stimulatory and suppressive motifs, and the resultant modulation of the immune system. Results suggest that both CpG and suppressive ODN may find use as therapeutic agents.

引用

页码：112 / 123

页数：12

共 42 条

[11] CpG-DNA-specific activation of antigen-presenting cells requires stress kinase activity and is preceded by non-specific endocytosis and endosomal maturation [J].

Häcker, H ;

Mischak, H ;

Miethke, T ;

Liptay, S ;

Schmid, R ;

Sparwasser, T ;

Heeg, K ;

Lipford, GB ;

Wagner, H .

EMBO JOURNAL, 1998, 17 (21) :6230-6240

[12] IN-VITRO INHIBITION OF MURINE IFN-GAMMA PRODUCTION BY PHOSPHOROTHIOATE DEOXYGUANOSINE OLIGOMERS [J].

HALPERN, MD ;

PISETSKY, DS .

IMMUNOPHARMACOLOGY, 1995, 29 (01) :47-52

[13] G-quadruplex DNA: a potential target for anti-cancer drug design [J].

Han, HY ;

Hurley, LH .

TRENDS IN PHARMACOLOGICAL SCIENCES, 2000, 21 (04) :136-142

[14] A Toll-like receptor recognizes bacterial DNA [J].

Hemmi, H ;

Takeuchi, O ;

Kawai, T ;

Kaisho, T ;

Sato, S ;

Sanjo, H ;

Matsumoto, M ;

Hoshino, K ;

Wagner, H ;

Takeda, K ;

Akira, S .

NATURE, 2000, 408 (6813) :740-745

[15] Immune recognition of foreign DNA: A cure for bioterrorism? [J].

Klinman, DM ;

Verthelyi, D ;

Takeshita, F ;

Ishii, KJ .

IMMUNITY, 1999, 11 (02) :123-129

[16] Repeated administration of synthetic oligodeoxynucleotides expressing CpG motifs provides long-term protection against bacterial infection [J].

Klinman, DM ;

Conover, J ;

Coban, C .

INFECTION AND IMMUNITY, 1999, 67 (11) :5658-5663

[17]

Klinman DM, 1997, J IMMUNOL, V158, P3635

[18] CpG motifs present in bacterial DNA rapidly induce lymphocytes to secrete interleukin 6, interleukin 12, and interferon gamma [J].

Klinman, DM ;

Yi, AK ;

Beaucage, SL ;

Conover, J ;

Krieg, AM .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (07) :2879-2883

[19]

KLINMAN DM, 1994, CURRENT PROTOCOLS IM

[20] CPG MOTIFS IN BACTERIAL-DNA TRIGGER DIRECT B-CELL ACTIVATION [J].

KRIEG, AM ;

YI, AK ;

MATSON, S ;

WALDSCHMIDT, TJ ;

BISHOP, GA ;

TEASDALE, R ;

KORETZKY, GA ;

KLINMAN, DM .

NATURE, 1995, 374 (6522) :546-549

← 1 2 3 4 5 →