Transcriptional therapy with the histone deacetylase inhibitor trichostatin A ameliorates experimental autoimmune encephalomyelitis

Sandra Camelo; Antonio H. Iglesias; Daehee Hwang; Brice Due; Hoon Ryu; Karen Smith; Steven G. Gray; Jaime Imitola; German Duran; Basel Assaf; Brett Langley; Samia J. Khoury; George Stephanopoulos; Umberto De Girolami; Rajiv R. Ratan; Robert J. Ferrante; Fernando Dangond

doi:10.1016/j.jneuroim.2005.02.022

Transcriptional therapy with the histone deacetylase inhibitor trichostatin A ameliorates experimental autoimmune encephalomyelitis

Sandra Camelo, Antonio H. Iglesias, Daehee Hwang, Brice Due, Hoon Ryu, Karen Smith, Steven G. Gray, Jaime Imitola, German Duran, Basel Assaf, Brett Langley, Samia J. Khoury, George Stephanopoulos, Umberto De Girolami, Rajiv R. Ratan, Robert J. Ferrante, Fernando Dangond

Research output: Contribution to journal › Article › peer-review

248 Scopus citations

Abstract

We demonstrate that the histone deacetylase (HDAC) inhibitor drug trichostatin A (TSA) reduces spinal cord inflammation, demyelination, neuronal and axonal loss and ameliorates disability in the relapsing phase of experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS). TSA up-regulates antioxidant, anti-excitotoxicity and pro-neuronal growth and differentiation mRNAs. TSA also inhibits caspase activation and down-regulates gene targets of the pro-apoptotic E2F transcription factor pathway. In splenocytes, TSA reduces chemotactic, pro-Th1 and pro-proliferative mRNAs. A transcriptional imbalance in MS may contribute to immune dysregulation and neurodegeneration, and we identify HDAC inhibition as a transcriptional intervention to ameliorate this imbalance.

Original language	English (US)
Pages (from-to)	10-21
Number of pages	12
Journal	Journal of Neuroimmunology
Volume	164
Issue number	1-2
DOIs	https://doi.org/10.1016/j.jneuroim.2005.02.022
State	Published - Jul 2005
Externally published	Yes

Keywords

Experimental autoimmune encephalomyelitis
Histone deacetylase
Microarrays
Multiple sclerosis
Trichostatin A

ASJC Scopus subject areas

Immunology and Allergy
Immunology
Neurology
Clinical Neurology

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10.1016/j.jneuroim.2005.02.022

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Camelo, S., Iglesias, A. H., Hwang, D., Due, B., Ryu, H., Smith, K., Gray, S. G., Imitola, J., Duran, G., Assaf, B., Langley, B., Khoury, S. J., Stephanopoulos, G., De Girolami, U., Ratan, R. R., Ferrante, R. J., & Dangond, F. (2005). Transcriptional therapy with the histone deacetylase inhibitor trichostatin A ameliorates experimental autoimmune encephalomyelitis. Journal of Neuroimmunology, 164(1-2), 10-21. https://doi.org/10.1016/j.jneuroim.2005.02.022

Camelo, S, Iglesias, AH, Hwang, D, Due, B, Ryu, H, Smith, K, Gray, SG, Imitola, J, Duran, G, Assaf, B, Langley, B, Khoury, SJ, Stephanopoulos, G, De Girolami, U, Ratan, RR, Ferrante, RJ & Dangond, F 2005, 'Transcriptional therapy with the histone deacetylase inhibitor trichostatin A ameliorates experimental autoimmune encephalomyelitis', Journal of Neuroimmunology, vol. 164, no. 1-2, pp. 10-21. https://doi.org/10.1016/j.jneuroim.2005.02.022

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title = "Transcriptional therapy with the histone deacetylase inhibitor trichostatin A ameliorates experimental autoimmune encephalomyelitis",

abstract = "We demonstrate that the histone deacetylase (HDAC) inhibitor drug trichostatin A (TSA) reduces spinal cord inflammation, demyelination, neuronal and axonal loss and ameliorates disability in the relapsing phase of experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS). TSA up-regulates antioxidant, anti-excitotoxicity and pro-neuronal growth and differentiation mRNAs. TSA also inhibits caspase activation and down-regulates gene targets of the pro-apoptotic E2F transcription factor pathway. In splenocytes, TSA reduces chemotactic, pro-Th1 and pro-proliferative mRNAs. A transcriptional imbalance in MS may contribute to immune dysregulation and neurodegeneration, and we identify HDAC inhibition as a transcriptional intervention to ameliorate this imbalance.",

keywords = "Experimental autoimmune encephalomyelitis, Histone deacetylase, Microarrays, Multiple sclerosis, Trichostatin A",

author = "Sandra Camelo and Iglesias, {Antonio H.} and Daehee Hwang and Brice Due and Hoon Ryu and Karen Smith and Gray, {Steven G.} and Jaime Imitola and German Duran and Basel Assaf and Brett Langley and Khoury, {Samia J.} and George Stephanopoulos and {De Girolami}, Umberto and Ratan, {Rajiv R.} and Ferrante, {Robert J.} and Fernando Dangond",

note = "Funding Information: This work was supported by NIH 1KO8-CA80084 and R21-NS41623 (F.D.) and NIH NS045242, NS045806 and the Veterans Administration (R.J.F.). Thanks to the BWH GATC Center for technical support.",

year = "2005",

month = jul,

doi = "10.1016/j.jneuroim.2005.02.022",

language = "English (US)",

volume = "164",

pages = "10--21",

journal = "Advances in Neuroimmunology",

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T1 - Transcriptional therapy with the histone deacetylase inhibitor trichostatin A ameliorates experimental autoimmune encephalomyelitis

AU - Camelo, Sandra

AU - Iglesias, Antonio H.

AU - Hwang, Daehee

AU - Due, Brice

AU - Ryu, Hoon

AU - Smith, Karen

AU - Gray, Steven G.

AU - Imitola, Jaime

AU - Duran, German

AU - Assaf, Basel

AU - Langley, Brett

AU - Khoury, Samia J.

AU - Stephanopoulos, George

AU - De Girolami, Umberto

AU - Ratan, Rajiv R.

AU - Ferrante, Robert J.

AU - Dangond, Fernando

N1 - Funding Information: This work was supported by NIH 1KO8-CA80084 and R21-NS41623 (F.D.) and NIH NS045242, NS045806 and the Veterans Administration (R.J.F.). Thanks to the BWH GATC Center for technical support.

PY - 2005/7

Y1 - 2005/7

N2 - We demonstrate that the histone deacetylase (HDAC) inhibitor drug trichostatin A (TSA) reduces spinal cord inflammation, demyelination, neuronal and axonal loss and ameliorates disability in the relapsing phase of experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS). TSA up-regulates antioxidant, anti-excitotoxicity and pro-neuronal growth and differentiation mRNAs. TSA also inhibits caspase activation and down-regulates gene targets of the pro-apoptotic E2F transcription factor pathway. In splenocytes, TSA reduces chemotactic, pro-Th1 and pro-proliferative mRNAs. A transcriptional imbalance in MS may contribute to immune dysregulation and neurodegeneration, and we identify HDAC inhibition as a transcriptional intervention to ameliorate this imbalance.

AB - We demonstrate that the histone deacetylase (HDAC) inhibitor drug trichostatin A (TSA) reduces spinal cord inflammation, demyelination, neuronal and axonal loss and ameliorates disability in the relapsing phase of experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS). TSA up-regulates antioxidant, anti-excitotoxicity and pro-neuronal growth and differentiation mRNAs. TSA also inhibits caspase activation and down-regulates gene targets of the pro-apoptotic E2F transcription factor pathway. In splenocytes, TSA reduces chemotactic, pro-Th1 and pro-proliferative mRNAs. A transcriptional imbalance in MS may contribute to immune dysregulation and neurodegeneration, and we identify HDAC inhibition as a transcriptional intervention to ameliorate this imbalance.

KW - Experimental autoimmune encephalomyelitis

KW - Histone deacetylase

KW - Microarrays

KW - Multiple sclerosis

KW - Trichostatin A

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Transcriptional therapy with the histone deacetylase inhibitor trichostatin A ameliorates experimental autoimmune encephalomyelitis

Abstract

Keywords

ASJC Scopus subject areas

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