The histone deacetylase inhibitor suberoylanilide hydroxamic acid attenuates human astrocyte neurotoxicity induced by interferon-γ
Identifieur interne : 001107 ( Main/Exploration ); précédent : 001106; suivant : 001108The histone deacetylase inhibitor suberoylanilide hydroxamic acid attenuates human astrocyte neurotoxicity induced by interferon-γ
Auteurs : Andis Klegeris [Canada] ; Patrick L. Mcgeer [Canada]Source :
- Journal of Neuroinflammation [ 1742-2094 ] ; 2012.
Abstract
Increasing evidence shows that the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) possesses potent anti-inflammatory and immunomodulatory properties. It is tempting to evaluate the potential of SAHA as a therapeutic agent in various neuroinflammatory and neurodegenerative disorders.
We examined the effects of SAHA on interferon (IFN)-γ-induced neurotoxicity of human astrocytes and on IFN-γ-induced phosphorylation of signal transducer and activator of transcription (STAT) 3 in human astrocytes. We also studied the effects of SAHA on the astrocytic production of two representative IFN-γ-inducible inflammatory molecules, namely IFN-γ-inducible T cell α chemoattractant (I-TAC) and intercellular adhesion molecule-1 (ICAM-1).
SAHA significantly attenuated the toxicity of astrocytes activated by IFN-γ towards SH-SY5Y human neuronal cells. In the IFN-γ-activated astrocytes, SAHA reduced the STAT3 phosphorylation. SAHA also inhibited the IFN-γ-induced astrocytic production of I-TAC, but not ICAM-1. These results indicate that SAHA suppresses IFN-γ-induced neurotoxicity of human astrocytes through inhibition of the STAT3 signaling pathway.
Due to its anti-neurotoxic and anti-inflammatory properties, SAHA appears to have the therapeutic or preventive potential for a wide range of neuroinflammatory disorders associated with activated astrocytes.
Url:
DOI: 10.1186/1742-2094-9-113
PubMed: 22647614
PubMed Central: 3410763
Affiliations:
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">The histone deacetylase inhibitor suberoylanilide hydroxamic acid attenuates human astrocyte neurotoxicity induced by interferon-γ</title><author><name sortKey="Klegeris, Andis" sort="Klegeris, Andis" uniqKey="Klegeris A" first="Andis" last="Klegeris">Andis Klegeris</name><affiliation wicri:level="1"><nlm:aff id="I2">Department of Biology, I.K. Barber School of Arts and Sciences, the University of British Columbia Okanagan, 3333 University Way, Kelowna, BC, V1V 1 V7, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Biology, I.K. Barber School of Arts and Sciences, the University of British Columbia Okanagan, 3333 University Way, Kelowna, BC, V1V 1 V7</wicri:regionArea><wicri:noRegion>V1V 1 V7</wicri:noRegion></affiliation></author><author><name sortKey="Mcgeer, Patrick L" sort="Mcgeer, Patrick L" uniqKey="Mcgeer P" first="Patrick L" last="Mcgeer">Patrick L. Mcgeer</name><affiliation wicri:level="1"><nlm:aff id="I1">Kinsmen Laboratory of Neurological Research, Department of Psychiatry, the University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC, V6T 1Z3, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Kinsmen Laboratory of Neurological Research, Department of Psychiatry, the University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC, V6T 1Z3</wicri:regionArea><wicri:noRegion>V6T 1Z3</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">22647614</idno><idno type="pmc">3410763</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3410763</idno><idno type="RBID">PMC:3410763</idno><idno type="doi">10.1186/1742-2094-9-113</idno><date when="2012">2012</date><idno type="wicri:Area/Pmc/Corpus">000501</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000501</idno><idno type="wicri:Area/Pmc/Curation">000501</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000501</idno><idno type="wicri:Area/Pmc/Checkpoint">000749</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000749</idno><idno type="wicri:Area/Ncbi/Merge">001158</idno><idno type="wicri:Area/Ncbi/Curation">001158</idno><idno type="wicri:Area/Ncbi/Checkpoint">001158</idno><idno type="wicri:Area/Main/Merge">001127</idno><idno type="wicri:Area/Main/Curation">001107</idno><idno type="wicri:Area/Main/Exploration">001107</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">The histone deacetylase inhibitor suberoylanilide hydroxamic acid attenuates human astrocyte neurotoxicity induced by interferon-γ</title><author><name sortKey="Klegeris, Andis" sort="Klegeris, Andis" uniqKey="Klegeris A" first="Andis" last="Klegeris">Andis Klegeris</name><affiliation wicri:level="1"><nlm:aff id="I2">Department of Biology, I.K. Barber School of Arts and Sciences, the University of British Columbia Okanagan, 3333 University Way, Kelowna, BC, V1V 1 V7, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Biology, I.K. Barber School of Arts and Sciences, the University of British Columbia Okanagan, 3333 University Way, Kelowna, BC, V1V 1 V7</wicri:regionArea><wicri:noRegion>V1V 1 V7</wicri:noRegion></affiliation></author><author><name sortKey="Mcgeer, Patrick L" sort="Mcgeer, Patrick L" uniqKey="Mcgeer P" first="Patrick L" last="Mcgeer">Patrick L. Mcgeer</name><affiliation wicri:level="1"><nlm:aff id="I1">Kinsmen Laboratory of Neurological Research, Department of Psychiatry, the University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC, V6T 1Z3, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Kinsmen Laboratory of Neurological Research, Department of Psychiatry, the University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC, V6T 1Z3</wicri:regionArea><wicri:noRegion>V6T 1Z3</wicri:noRegion></affiliation></author></analytic><series><title level="j">Journal of Neuroinflammation</title><idno type="eISSN">1742-2094</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Backgrounds</title><p>Increasing evidence shows that the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) possesses potent anti-inflammatory and immunomodulatory properties. It is tempting to evaluate the potential of SAHA as a therapeutic agent in various neuroinflammatory and neurodegenerative disorders.</p></sec><sec><title>Methods</title><p>We examined the effects of SAHA on interferon (IFN)-γ-induced neurotoxicity of human astrocytes and on IFN-γ-induced phosphorylation of signal transducer and activator of transcription (STAT) 3 in human astrocytes. We also studied the effects of SAHA on the astrocytic production of two representative IFN-γ-inducible inflammatory molecules, namely IFN-γ-inducible T cell α chemoattractant (I-TAC) and intercellular adhesion molecule-1 (ICAM-1).</p></sec><sec><title>Results</title><p>SAHA significantly attenuated the toxicity of astrocytes activated by IFN-γ towards SH-SY5Y human neuronal cells. In the IFN-γ-activated astrocytes, SAHA reduced the STAT3 phosphorylation. SAHA also inhibited the IFN-γ-induced astrocytic production of I-TAC, but not ICAM-1. These results indicate that SAHA suppresses IFN-γ-induced neurotoxicity of human astrocytes through inhibition of the STAT3 signaling pathway.</p></sec><sec><title>Conclusion</title><p>Due to its anti-neurotoxic and anti-inflammatory properties, SAHA appears to have the therapeutic or preventive potential for a wide range of neuroinflammatory disorders associated with activated astrocytes.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Grant, S" uniqKey="Grant S">S Grant</name></author><author><name sortKey="Easley, C" uniqKey="Easley C">C Easley</name></author><author><name sortKey="Kirkpatrick, P" uniqKey="Kirkpatrick P">P Kirkpatrick</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lemoine, M" uniqKey="Lemoine M">M Lemoine</name></author><author><name sortKey="Younes, A" uniqKey="Younes A">A Younes</name></author></analytic></biblStruct><biblStruct><analytic><author><name 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uniqKey="Klegeris A" first="Andis" last="Klegeris">Andis Klegeris</name></noRegion><name sortKey="Mcgeer, Patrick L" sort="Mcgeer, Patrick L" uniqKey="Mcgeer P" first="Patrick L" last="Mcgeer">Patrick L. 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