Regulation of the severity of neuroinflammation and demyelination by TLR‐ASK1‐p38 pathway
Open Access
- 10 November 2010
- journal article
- research article
- Published by Springer Science and Business Media LLC in EMBO Molecular Medicine
- Vol. 2 (12), 504-515
- https://doi.org/10.1002/emmm.201000103
Abstract
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.This publication has 47 references indexed in Scilit:
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