Treatment of autoimmune encephalomyelitis with a histone deacetylase inhibitor: Analyzing the role of immune-response genes

Free Neuropathology

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Title Treatment of autoimmune encephalomyelitis with a histone deacetylase inhibitor: Analyzing the role of immune-response genes
 
Creator Jayaraman, Arathi
Avgush, Karen
Kulam, Rashad
Soni, Advait
Khan, Areeb
Kerdjoudj, Mourad
Jayaraman, Sundararajan
 
Description We have previously shown that treatment of female NOD mice with a potent nonselective histone deacetylase inhibitor attenuated experimental autoimmune encephalomyelitis, a model for progressive multiple sclerosis. Herein we show that immunization with the MOG35-55 peptide induced prolonged upregulation of genes encoding interleukin 17A (IL-17A), aryl hydrocarbon receptor, and histone deacetylase 11 in the spinal cord whereas the subunits of IL-27, IL-27p28 and IL-27ebi3 were significantly increased in secondary lymphoid organs after a lag period. Interestingly, the nitric oxide synthase gene was prominently expressed in both of these anatomic compartments following immunization. Treatment with the histone modifier repressed the transcription of all of these genes induced by immunization. Moreover, the drug suppressed the steady-state levels of the migration inhibitory factor and CD274 genes in both the spinal cord and peripheral lymphoid tissues. At the same time, the CD39 gene was downregulated only in secondary lymphoid organs. Paradoxically, the epigenetic drug enhanced the expression of Declin-1 in the spinal cord, suggesting a protective role in neuronal disease. Immunization profoundly enhanced transcription of the chemokine CCL2 in the secondary lymphoid tissues without a corresponding increase in the translation of CCL2 protein. Histone hyperacetylation neither altered the transcription of CCL2 nor its cognate receptor CCR2 in the central nervous system and peripheral lymphoid tissues. Surprisingly, the drug did not exert modulatory influence on most other immune response-related genes previously implicated in encephalomyelitis. Nevertheless, our data uncover several potential molecular targets for the intervention of experimental autoimmune encephalomyelitis that have implications for the treatment of progressive multiple sclerosis.
 
Publisher Free Neuropathology
Free Neuropathology
 
Date 2020-07-14
 
Type info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
Original Paper
 
Format text/html
application/pdf
application/pdf
 
Identifier https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2819
10.17879/freeneuropathology-2020-2819
 
Source Free Neuropathology; Bd. 1 (2020); 19
Free Neuropathology; Vol 1 (2020); 19
2699-4445
 
Language eng
 
Relation https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2819/2836
https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2819/2829
https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2819/2830
urn:nbn:de:hbz:6:3-freeneuropathology-2020-28298
 
Rights Copyright (c) 2020 Arathi Jayaraman, Karen Avgush, Rashad Kulam, Advait Soni, Areeb Khan, Mourad Kerdjoudj, Sundararajan Jayaraman
http://creativecommons.org/licenses/by/4.0
 

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