Mammalian telomeric DNA suppresses endotoxin-induced uveitis.

The Journal of Biological Chemistry
Fuat C YagciIhsan Gursel

Abstract

Telomeric regions of mammalian chromosomes contain suppressive TTAGGG motifs that inhibit several proinflammatory and Th1-biased immune responses. Synthetic oligodeoxynucleotides (ODN) expressing suppressive motifs can reproduce the down-regulatory activity of mammalian telomeric repeats and have proven effective in the prevention and treatment of several autoimmune and autoinflammatory diseases. Endotoxin-induced uveitis (EIU) is an established animal model of acute ocular inflammation induced by LPS administration. Augmented expression of proinflammatory cytokines/chemokines such as TNFalpha, IL-6, and MCP1 and bactericidal nitric oxide production mediated by LPS contribute to the development of EIU. Suppressing these mediators using agents that are devoid of undesirable systemic side effects may help prevent the development of EIU. This study demonstrates the selective down-regulatory role of suppressive ODN after (i) local or (ii) systemic treatment in EIU-induced rabbits and mice. Our results indicate that suppressive ODN down-regulate at both the transcript and protein levels of several proinflammatory cytokines and chemokines as well as nitric oxide and co-stimulatory surface marker molecules when administrated prior to,...Continue Reading

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Citations

Oct 15, 2014·International Immunopharmacology·Christian BodeDennis M Klinman
Jan 19, 2016·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Defne BayikDennis M Klinman
Nov 19, 2015·Proceedings of the National Academy of Sciences of the United States of America·Zhuo WangPaul M Lieberman
May 7, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ana P GirolSonia M Oliani

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