کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3065668 1580483 2007 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Inhibition of Smad7, a negative regulator of TGF-beta signaling, suppresses autoimmune encephalomyelitis
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی ایمونولوژی
پیش نمایش صفحه اول مقاله
Inhibition of Smad7, a negative regulator of TGF-beta signaling, suppresses autoimmune encephalomyelitis
چکیده انگلیسی

We studied the role of the Transforming growth factor (TGF)-β 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 autoimmune CNS inflammation, targeting TGF-β signaling without TGF-β-associated toxicity.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Neuroimmunology - Volume 187, Issues 1–2, July 2007, Pages 61–73
نویسندگان
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