Kleiter, Ingo and Pedre, Xiomara and Mueller, Andre M. and Poeschl, Peter and Couillard-Despres, Sebastien and Spruss, Thilo and Bogdahn, Ulrich and Glegerich, Gerhard and Steinbrecher, Andreas (2007) Inhibition of Smad7, a negative regulator of TGF-beta signaling, suppresses autoimmune encephalomyelitis. JOURNAL OF NEUROIMMUNOLOGY, 187 (1-2). pp. 61-73. ISSN 0165-5728,
Full text not available from this repository. (Request a copy)Abstract
We studied the role of the Transforming growth factor (TGF)-beta signaling antagonist Smad7 in autoimmune central nervous system (CNS) inflammation by using specific antisense oligonucleotides (Smad7-as). Elevated Smad7 protein expression was found in the spinal cord of SJL/J mice and DA rats with experimental autoimmune encephalomyelitis (EAE) and in effector T cells upon antigen stimulation. Smad7-as specifically decreased Smad7 mRNA and protein in cell lines and in ex-vivo-treated primary mouse lymph node cells (LNC). LNC exposed to Smad7-as during secondary activation showed reduced proliferation and encephalitogenicity. After systemic administration, Smad7-as ameliorated clinical signs of active and adoptively transferred EAE, diminished CNS inflammation, and reduced Smad7 protein levels in the brain. Smad7-as was found to be incorporated by peritoneal macrophages as well as by cells of the liver, kidneys, and peripheral lymph nodes. Importantly, Smad7-as treatment was not toxic and did not increase extracellular matrix formation. Smad7 inhibition thus represents a novel systemic treatment strategy for autommume CNS inflammation, targeting TGF-beta signaling without TGF-beta-associated toxicity. (c) 2007 Elsevier B.V. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GROWTH-FACTOR-BETA; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; MYELIN BASIC-PROTEIN; T-CELLS; IMMUNE-RESPONSES; DOWN-REGULATION; IN-VIVO; FACTOR-BETA-1; ACTIVATION; MECHANISMS; autoimmunity; inflammation; T cell; TGF-beta; Smad7; antisense oligonucleotide |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Neurologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 04 Dec 2020 10:24 |
| Last Modified: | 04 Dec 2020 10:24 |
| URI: | https://pred.uni-regensburg.de/id/eprint/32561 |
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