Suppressive oligodeoxynucleotides protect mice from lethal endotoxic shock.

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2005-04-15

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Shirota, H
Gursel, I
Gürsel, Mayda
Klinman, DM

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Endotoxic shock is a life-threatening condition caused by exposure to bacterial LPS. LPS triggers the release of acute phase, proinflammatory, and Th1 cytokines that facilitate the development of endotoxic shock. Synthetic oligodeoxynucleotides (ODN) expressing suppressive TTAGGG motifs effectively down-regulate the production of proinflammatory and Th1 cytokines elicited by a variety of immune stimuli. The current results demonstrate that suppressive ODN protect mice from LPS-induced endotoxic shock. Underlying this protective effect is the ability of suppressive ODN to bind to and prevent the phosphorylation of STAT1 and STAT4, thereby blocking the signaling cascade mediated by LPS-induced IFN- and IL-12. These findings suggest that suppressive ODN might be of use in the treatment of endotoxic shock.

Subject Keywords

Immunology

URI

https://hdl.handle.net/11511/34958

Journal

Journal of immunology (Baltimore, Md. : 1950)

DOI

https://doi.org/10.4049/jimmunol.174.8.4579

Collections

Department of Biology, Article

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Suppressive oligodeoxynucleotides inhibit Th1 differentiation by blocking IFN-gamma- and IL-12-mediated signaling. Shirota, H; Gürsel, Mayda; Klinman, DM (The American Association of Immunologists, 2004-10-15) Repetitive TTAGGG motifs present at high frequency in mammalian telomeres can suppress Th1-mediated immune responses. Synthetic oligonucleotides (ODN) containing TTAGGG motifs mimic this activity and have proven effective in the prevention/ treatment of certain Th1-dependent autoimmune diseases. This work explores the mechanism by which suppressive ODN block the induction of Th1 immunity. Findings indicate that these ODN inhibit IFN- -induced STAT1 phosphorylation and IL-12- induced STAT3 and STAT4 phosphor...
Repetitive elements in mammalian telomeres suppress bacterial DNA-induced immune activation. Gursel, I; Gürsel, Mayda; Yamada, H; Ishii, KJ; Takeshita, F; Klinman, DM (The American Association of Immunologists, 2003-08-01) Bacterial DNA contains immunostimulatory CpG motifs that trigger an innate immune response capable of promoting host survival following infectious challenge. Yet CpG-driven immune activation may also have deleterious consequences, ranging from autoimmune disease to death. We find that repetitive elements present at high frequency in mammalian telomeres, but rare in bacteria, down-regulate CpG-induced immune activation. Suppressive activity correlates with the ability of telomeric TTAGGG repeats to form G-te...
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Citation Formats

H. Shirota, I. Gursel, M. Gürsel, and D. Klinman, “Suppressive oligodeoxynucleotides protect mice from lethal endotoxic shock.,” Journal of immunology (Baltimore, Md. : 1950), pp. 4579–83, 2005, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/34958.