Regulation of the severity of neuroinflammation and demyelination by TLR‐ASK1‐p38 pathway
| Autor: | Kuniko Kohyama, Hong Ji, Thomas Rückle, Xiaoli Guo, Yoh Matsumoto, Hidenori Ichijo, Chikako Harada, Montserrat Camps, Kazuhiko Namekata, Atsushi Matsuzawa, Mathilde Muzerelle, Atsuko Kimura, Catherine Jorand-Lebrun, Takayuki Harada, Dominique Swinnen, Pierre Alain Vitte |
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| Rok vydání: | 2010 |
| Předmět: |
Male
MAPK/ERK pathway Chemokine glia chemokines Hashimoto Disease Biology MAP Kinase Kinase Kinase 5 p38 Mitogen-Activated Protein Kinases Rats Sprague-Dawley Mice medicine Animals Humans ASK1 Enzyme Inhibitors Protein kinase A Research Articles Neuroinflammation Brain Diseases Microglia Kinase Toll-Like Receptors Experimental autoimmune encephalomyelitis medicine.disease Rats Mice Inbred C57BL Disease Models Animal medicine.anatomical_structure Gene Expression Regulation Immunology Cancer research biology.protein Encephalitis Molecular Medicine Female demyelination Neuroglia Demyelinating Diseases Signal Transduction |
| Zdroj: | EMBO Molecular Medicine |
| ISSN: | 1757-4684 1757-4676 |
| Popis: | Apoptosis signal-regulating kinase 1 (ASK1) is an evolutionarily conserved mitogen-activated protein kinase (MAPK) kinase kinase which plays important roles in stress and immune responses. Here, we show that ASK1 deficiency attenuates neuroinflammation in experimental autoimmune encephalomyelitis (EAE), without affecting the proliferation capability of T cells. Moreover, we found that EAE upregulates expression of Toll-like receptors (TLRs) in activated astrocytes and microglia, and that TLRs can synergize with ASK1-p38 MAPK signalling in the release of key chemokines from astrocytes. Consequently, oral treatment with a specific small molecular weight inhibitor of ASK1 suppressed EAE-induced autoimmune inflammation in both spinal cords and optic nerves. These results suggest that the TLR-ASK1-p38 pathway in glial cells may serve as a valid therapeutic target for autoimmune demyelinating disorders including multiple sclerosis. |
| Databáze: | OpenAIRE |
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