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Induction of Experimental Autoimmune Encephalomyelitis in Mice and Evaluation of the Disease-dependent Distribution of Immune Cells in Various Tissues
Published on: May 8, 2016
Microarray analysis of gene expression in multiple sclerosis and EAE identifies 5-lipoxygenase as a component of
L W Whitney1, S K Ludwin, H F McFarland
1Molecular Immunology Section, Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, NIH, Bldg. 10/Rm 5B-16, Bethesda, MD 20892-1400, USA.
Abstract:
Multiple sclerosis (MS) is a demyelinating disease of the central nervous system characterized by lesions that are areas of blood-brain barrier breakdown, inflammation and myelin damage. To identify genes that contribute to lesion pathology, we have compared gene expression in MS lesions and in brains of mice with experimental allergic encephalomyelitis (EAE) with that in normal white matter. Gene expression was analyzed by cDNA microarrays consisting of 2798 human genes. One of the genes found to be upregulated in both MS lesions and EAE brains was 5-lipoxygenase (5-LO), a key enzyme in the biosynthesis of the proinflammatory leukotrienes. The presence of 5-LO in MS lesions was confirmed by immunohistochemistry and indicated that 5-LO was primarily contained within macrophages. Although these findings are not specific for MS, they identify a potentially important component of pro-inflammatory activity in the demyelinating process in MS and suggest a possible target for anti-inflammatory therapy in MS.
Insights
Researchers identified 5-lipoxygenase (5-LO), an enzyme involved in inflammation, as upregulated in multiple sclerosis (MS) lesions. This finding suggests 5-LO may be a therapeutic target for MS treatment.
Area of Science:
- Neuroscience
- Immunology
- Genetics
Background:
- Multiple sclerosis (MS) is a central nervous system demyelinating disease.
- MS lesions involve blood-brain barrier breakdown, inflammation, and myelin damage.
Purpose of the Study:
- To identify genes contributing to MS lesion pathology.
- To compare gene expression in MS lesions and EAE mouse models with normal white matter.
Main Methods:
- Gene expression analysis using cDNA microarrays (2798 human genes).
- Immunohistochemistry to confirm protein presence in lesions.
Main Results:
- 5-lipoxygenase (5-LO), a key enzyme in pro-inflammatory leukotriene biosynthesis, was upregulated in both MS lesions and EAE mouse brains.
- Immunohistochemistry confirmed 5-LO presence primarily within macrophages in MS lesions.
Conclusions:
- Upregulated 5-LO is a potentially significant factor in MS inflammatory activity and demyelination.
- 5-LO presents a possible therapeutic target for anti-inflammatory strategies in MS.
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