| First Author | Kleiter I | Year | 2007 |
| Journal | J Neuroimmunol | Volume | 187 |
| Issue | 1-2 | Pages | 61-73 |
| PubMed ID | 17553571 | Mgi Jnum | J:128877 |
| Mgi Id | MGI:3768216 | Doi | 10.1016/j.jneuroim.2007.04.014 |
| Citation | Kleiter I, et al. (2007) Inhibition of Smad7, a negative regulator of TGF-beta signaling, suppresses autoimmune encephalomyelitis. J Neuroimmunol 187(1-2):61-73 |
| abstractText | 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 autoimmune CNS inflammation, targeting TGF-beta signaling without TGF-beta-associated toxicity. |
