Journal
JOURNAL OF THE NEUROLOGICAL SCIENCES
Volume 343, Issue 1-2, Pages 69-75Publisher
ELSEVIER
DOI: 10.1016/j.jns.2014.05.034
Keywords
Rho kinase inhibitor; Fasudil; Experimental autoimmune encephalomyelitis; Astrocytes; Cytokines; Chemokines
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Funding
- National Natural Science Foundation of China [81070957, 81272163, 30972715]
- Shanxi University of Traditional Chinese Medicine [2011PY-1]
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Multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), are autoimmune diseases characterized by the immune-mediated demyelination and neurodegeneration of the CNS. Our previous studies showed that Rho kinase inhibitor Fasudil can delay onset and ameliorate severity of EAE, accompanied by the improvement in myelinafion and the inhibition of inflammatory responses in the CNS. In this study, we found that Fasudil inhibited the migration of T cells indirectly by affecting the production of inflammatory factors and the expression of chemokines in astrocytes functions, indicating that Fasudil treatment reduced inflammatory cytokines such as TNF-alpha and IL-6, reactive oxygen species (NO) and chemoldnes like MIP-3 alpha. (CCL-20), RANTES (CCL5), MIP-1 alpha (CCL-3) and MCP-1 (CCL2) in vitro, and blocked the chemotaxis of reactive mononuclear cells in EAE mice. Further studies found that Fasudil treatment reduced the infiltration and accumulation of pathogenic T cells into the CNS. Astrocytes expressing GFAP and CCL-20 were inhibited in Fasudil-treated EAE compared with control mice. These results demonstrate that Fasudil alleviates the pathogenesis of EAE possibly by blocking astrocyte-derived chemokine-mediated migration of inflammatory macrophages and pathogenic T cells, and might be used to treat MS. (C) 2014 Published by Elsevier B.V.
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