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Endogenously regulated Dab2 worsens inflammatory injury in experimental autoimmune encephalomyelitis.
- Source :
-
Acta neuropathologica communications [Acta Neuropathol Commun] 2013 Jul 09; Vol. 1, pp. 32. Date of Electronic Publication: 2013 Jul 09. - Publication Year :
- 2013
-
Abstract
- Background: Neuroinflammation regulates both disease pathogenesis and repair in multiple sclerosis. In early multiple sclerosis lesion development, neuroinflammation causes demyelination and axonal injury, the likely final common determinant of disability. Here we report the identification of a novel neuroinflammatory mediator, Disabled-2 (Dab2). Dab2 is an intracellular adaptor protein with previously unknown function in the central nervous system.<br />Results: We report that Dab2 is up-regulated in lesional macrophages/microglia in the spinal cord in murine experimental autoimmune encephalomyelitis, a model of multiple sclerosis. We demonstrate that dab2 expression is positively correlated with experimental autoimmune encephalomyelitis disease severity during the acute disease phase. Furthermore, dab2-deficient mice have a less severe experimental autoimmune encephalomyelitis disease course and suffer less neuroinflammation and less axonal injury than their wild-type littermates. We demonstrate that dab2 expression is strongly associated with the expression of inducible nitric oxide synthase. We further demonstrate that Dab2 is expressed at the protein level by macrophages in early acute human multiple sclerosis lesions and that this correlates with axonal injury.<br />Conclusions: Together, these results suggest that endogenous Dab2 exacerbates central nervous system inflammation, potentially acting to up-regulate reactive oxygen species expression in macrophages and microglia, and that it is of potential pathogenic relevance in Multiple Sclerosis.
- Subjects :
- Adaptor Proteins, Vesicular Transport genetics
Animals
Apoptosis Regulatory Proteins
Encephalomyelitis, Autoimmune, Experimental metabolism
Female
Interleukin-1beta metabolism
Macrophages immunology
Male
Mice, Inbred C57BL
Mice, Knockout
Microglia immunology
Multiple Sclerosis metabolism
Neuroimmunomodulation physiology
Nitric Oxide Synthase Type II metabolism
Severity of Illness Index
T-Lymphocytes physiology
Adaptor Proteins, Signal Transducing metabolism
Adaptor Proteins, Vesicular Transport metabolism
Encephalomyelitis, Autoimmune, Experimental immunology
Multiple Sclerosis immunology
Spinal Cord immunology
Tumor Suppressor Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2051-5960
- Volume :
- 1
- Database :
- MEDLINE
- Journal :
- Acta neuropathologica communications
- Publication Type :
- Academic Journal
- Accession number :
- 24252604
- Full Text :
- https://doi.org/10.1186/2051-5960-1-32