Attenuation of murine antigen-induced arthritis by treatment with a decoy oligodeoxynucleotide inhibiting signal transducer and activator of transcription-1 (STAT-1)

Arthritis Research & Therapy
Marion HückelR Bräuer

Abstract

The transcription factor STAT-1 (signal transducer and activator of transcription-1) plays a pivotal role in the expression of inflammatory gene products involved in the pathogenesis of arthritis such as various cytokines and the CD40/CD40 ligand (CD40/CD40L) receptor-ligand dyad. The therapeutic efficacy of a synthetic decoy oligodeoxynucleotide (ODN) binding and neutralizing STAT-1 was tested in murine antigen-induced arthritis (AIA) as a model for human rheumatoid arthritis (RA). The STAT-1 decoy ODN was injected intra-articularly in methylated bovine serum albumin (mBSA)-immunized mice 4 h before arthritis induction. Arthritis was evaluated by joint swelling measurement and histological evaluation and compared to treatment with mutant control ODN. Serum levels of pro-inflammatory cytokines, mBSA-specific antibodies and auto-antibodies against matrix constituents were assessed by enzyme-linked immunosorbent assay (ELISA). The transcription factor neutralizing efficacy of the STAT-1 decoy ODN was verified in vitro in cultured synoviocytes and macrophages. Single administration of STAT-1 decoy ODN dose-dependently suppressed joint swelling and histological signs of acute and chronic arthritis. Delayed-type hypersensitivity (DT...Continue Reading

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Citations

Apr 9, 2009·Basic Research in Cardiology·Tomislav StojanovicMarkus Hecker
Mar 6, 2013·The Journal of Biological Chemistry·Carla BocianDaniela G Seidler
Aug 2, 2013·Nature Reviews. Drug Discovery·Gabriella MiklossyJames Turkson
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Sep 24, 2013·JAK-STAT·Remi FagardFanny Baran-Marszak
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Dec 17, 2018·Yonsei Medical Journal·Seung Min JungJi Hyeon Ju
Nov 27, 2021·Signal Transduction and Targeted Therapy·Xiaoyi HuWei Wang

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Methods Mentioned

BETA
electrophoresis
ELISA
FCS
PCR

Software Mentioned

SPSS

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