Therapeutic applications and mechanisms underlying the activity of immunosuppressive oligonucleotides

Dennis M. Klinman, Debbie Tross, Sven Klaschik, Hidekazu Shirota, Takeshi Sato

研究成果: Conference contribution

28 被引用数 (Scopus)

抄録

Synthetic oligodeoxynucleotides (ODN) capable of "neutralizing" or "inhibiting" immune responses have been described. This review will focus on the properties of phosphorothioate ODN that mimic the immunosuppressive activity of the repetitive TTAGGG motifs present in mammalian telomeres. These TTAGGG multimers block the production of pro-inflammatory and T helper type 1 cytokines elicited when immune cells are activated by a wide variety of Toll-like receptor ligands, polyclonal activators, and antigens. Several mechanisms contribute to the suppressive activity of such ODN. Ongoing microarray studies indicate that suppressive ODN interfere with the phosphorylation of signal transducer and activator of transcription 1 (STAT1) and STAT4, thereby blocking the inflammation mediated by STAT-associated signaling cascades. In animal models, suppressive ODN can be used to prevent or treat diseases characterized by persistent immune activation, including collagen-induced arthritis, inflammatory arthritis, systemic lupus erythematosus, silicosis, and toxic shock. These findings suggest that TTAGGG multimers may find broad use in the treatment of diseases characterized by over-exuberant/persistent immune activation.

本文言語English
ホスト出版物のタイトルOligonucleotide Therapeutics Fourth Annual Meeting
出版社Blackwell Publishing Inc.
ページ80-88
ページ数9
ISBN(印刷版)9781573317580
DOI
出版ステータスPublished - 2009 9 1
外部発表はい

出版物シリーズ

名前Annals of the New York Academy of Sciences
1175
ISSN(印刷版)0077-8923
ISSN(電子版)1749-6632

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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