Abstract |
Synthetic suppressive oligodeoxynucleotides (ODNs) expressing TTAGGG motifs selectively reduce Th1 cytokine production and have been proven effective in T helper type 1 (Th1)-mediated autoimmune diseases. Concanavalin A (Con A)-induced hepatitis is characterized by elevated Th1 response. The present study aims to reveal a profound hepatoprotective effect of suppressive ODNs on Con A-induced hepatitis. BALB/c mice were injected with suppressive ODNs (i) prior to, (ii) simultaneously with, or (iii) after Con A challenge. The effect of suppressive ODNs on interferon (IFN)-γ and interleukin (IL)-4 expressions was determined. The effect of suppressive ODNs on signal modulators for Th1/Th2 pathway was examined. Our results showed that suppressive ODNs significantly reduced liver necroinflammatory injury and serum IFN-γ level, meanwhile increased IL-4 level. The mortality of suppressive ODNs-treated mice was reduced from 30% to 0% in 8h post Con A challenge. In the splenic lymphocytes, Western blot analysis showed that suppressive ODNs down-regulated the phosphorylation of signal transducer and activator of transcription 1 (STAT1) and STAT4, and suppressed up-regulation of T-bet, but did not impact the phosphorylation of STAT6 which are associated with a Th2 phenotype. Consistent with this in vivo observation, ELISA analysis demonstrated that suppressive ODNs inhibited IFN-γ, and augmented IL-4 production in the differentiation of naive T cells in vitro. We concluded that suppressive ODNs inhibit the development of Con A-induced hepatitis through down-regulation of the STAT1/4 and T-bet pathways and may be of use in the treatment of autoimmune or viral hepatitis in humans.
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Authors | Ning Li, Yue-Hui Liu, Sha-Ling Li, Chun-Yan Fu, Rong-Rong Zhou, Yan Huang, Xue-Gong Fan |
Journal | Immunology letters
(Immunol Lett)
Vol. 151
Issue 1-2
Pg. 54-60
(Mar 2013)
ISSN: 1879-0542 [Electronic] Netherlands |
PMID | 23470496
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2013 Elsevier B.V. All rights reserved. |
Chemical References |
- Immunosuppressive Agents
- Oligodeoxyribonucleotides
- STAT4 Transcription Factor
- Interleukin-4
- Interferon-gamma
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Topics |
- Animals
- Base Sequence
- Female
- Hepatitis, Animal
(chemically induced, immunology, prevention & control)
- Immunosuppressive Agents
(administration & dosage, chemistry, immunology)
- Interferon-gamma
(biosynthesis)
- Interleukin-4
(biosynthesis)
- Mice
- Nucleotide Motifs
- Oligodeoxyribonucleotides
(administration & dosage, chemistry, immunology)
- Phosphorylation
- STAT4 Transcription Factor
(metabolism)
- T-Lymphocyte Subsets
(immunology, metabolism)
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