NEUROTOXINS RELEASED FROM INTERFERON-GAMMA-STIMULATED HUMAN ASTROCYTES
Identifieur interne : 001058 ( Main/Exploration ); précédent : 001057; suivant : 001059NEUROTOXINS RELEASED FROM INTERFERON-GAMMA-STIMULATED HUMAN ASTROCYTES
Auteurs : M. Lee [Canada] ; E. Mcgeer [Canada] ; P. L. Mcgeer [Canada]Source :
- Neuroscience [ 0306-4522 ] ; 2013.
Descripteurs français
- Pascal (Inist)
- Wicri :
- topic : Homme.
English descriptors
- KwdEn :
Abstract
Astrocytes become activated in degenerative neurological diseases. In order to gain a greater understanding of the inflammatory factors released upon activation, we stimulated adult human astrocytes with interferon-gamma and examined the resultant conditioned medium (CM) for toxicity against differentiated human neuroblastoma SH-SY5Y cells. Cell death was measured by lactate dehydrogenase release assay. We then used various treatments of the media to determine the distribution and nature of the toxic components. Removal of interleukin-6 by a specific antibody reduced the toxicity by 22%. Blockade of proteases with an inhibitor cocktail reduced it by a further 22%. When oxygen-free radical production was blocked with NADPH oxidase inhibitors, the toxicity was reduced by 15.4%. When prostaglandin production was blocked by cyclooxygenase inhibitors, the toxicity of the CM was reduced by 14.5%. When glutamate was removed by treatment with glutamate decarboxylase, the toxicity was reduced by 10.3%. When the inhibitors were added together to the astrocyte culture, the total toxicity of the CM was reduced by 91%. This was in reasonable agreement with the 85.37% total obtained by adding the individual components. The data show that activated astrocytes release a specific combination of neurotoxic compounds. They suggest that effective anti-inflammatory treatment of such neurodegenerative diseases as Alzheimer's disease, Parkinson's disease and Amyotrophic lateral sclerosis could be improved by using an appropriate combination of anti-inflammatory agents instead of relying on any single agent.
Affiliations:
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Mcgeer</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Kinsmen Laboratory of Neurological Research, University of British Columbia, 2255 Wesbrook Mall</s1><s2>Vancouver, BC V6T 1Z3</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Vancouver, BC V6T 1Z3</wicri:noRegion></affiliation></author><author><name sortKey="Mcgeer, P L" sort="Mcgeer, P L" uniqKey="Mcgeer P" first="P. L." last="Mcgeer">P. L. Mcgeer</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Kinsmen Laboratory of Neurological Research, University of British Columbia, 2255 Wesbrook Mall</s1><s2>Vancouver, BC V6T 1Z3</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Vancouver, BC V6T 1Z3</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">13-0105662</idno><date when="2013">2013</date><idno type="stanalyst">PASCAL 13-0105662 INIST</idno><idno type="RBID">Pascal:13-0105662</idno><idno type="wicri:Area/PascalFrancis/Corpus">000114</idno><idno type="wicri:Area/PascalFrancis/Curation">000B18</idno><idno type="wicri:Area/PascalFrancis/Checkpoint">000067</idno><idno type="wicri:explorRef" wicri:stream="PascalFrancis" wicri:step="Checkpoint">000067</idno><idno type="wicri:doubleKey">0306-4522:2013:Lee M:neurotoxins:released:from</idno><idno type="wicri:Area/Main/Merge">001074</idno><idno type="wicri:Area/Main/Curation">001058</idno><idno type="wicri:Area/Main/Exploration">001058</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">NEUROTOXINS RELEASED FROM INTERFERON-GAMMA-STIMULATED HUMAN ASTROCYTES</title><author><name sortKey="Lee, M" sort="Lee, M" uniqKey="Lee M" first="M." last="Lee">M. Lee</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Kinsmen Laboratory of Neurological Research, University of British Columbia, 2255 Wesbrook Mall</s1><s2>Vancouver, BC V6T 1Z3</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Vancouver, BC V6T 1Z3</wicri:noRegion></affiliation></author><author><name sortKey="Mcgeer, E" sort="Mcgeer, E" uniqKey="Mcgeer E" first="E." last="Mcgeer">E. Mcgeer</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Kinsmen Laboratory of Neurological Research, University of British Columbia, 2255 Wesbrook Mall</s1><s2>Vancouver, BC V6T 1Z3</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Vancouver, BC V6T 1Z3</wicri:noRegion></affiliation></author><author><name sortKey="Mcgeer, P L" sort="Mcgeer, P L" uniqKey="Mcgeer P" first="P. L." last="Mcgeer">P. L. Mcgeer</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Kinsmen Laboratory of Neurological Research, University of British Columbia, 2255 Wesbrook Mall</s1><s2>Vancouver, BC V6T 1Z3</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Vancouver, BC V6T 1Z3</wicri:noRegion></affiliation></author></analytic><series><title level="j" type="main">Neuroscience</title><title level="j" type="abbreviated">Neuroscience</title><idno type="ISSN">0306-4522</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Neuroscience</title><title level="j" type="abbreviated">Neuroscience</title><idno type="ISSN">0306-4522</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Astrocyte</term><term>Gamma interferon</term><term>Glutamate</term><term>Human</term><term>Interleukin 6</term><term>Neurotoxicity</term><term>Neurotoxin</term><term>Oxidase</term><term>Peptidases</term><term>Prostaglandin-endoperoxide synthase</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Neurotoxine</term><term>Interféron gamma</term><term>Astrocyte</term><term>Interleukine 6</term><term>Oxidase</term><term>Prostaglandin-endoperoxide synthase</term><term>Glutamate</term><term>Peptidases</term><term>Neurotoxicité</term><term>Homme</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Homme</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Astrocytes become activated in degenerative neurological diseases. In order to gain a greater understanding of the inflammatory factors released upon activation, we stimulated adult human astrocytes with interferon-gamma and examined the resultant conditioned medium (CM) for toxicity against differentiated human neuroblastoma SH-SY5Y cells. Cell death was measured by lactate dehydrogenase release assay. We then used various treatments of the media to determine the distribution and nature of the toxic components. Removal of interleukin-6 by a specific antibody reduced the toxicity by 22%. Blockade of proteases with an inhibitor cocktail reduced it by a further 22%. When oxygen-free radical production was blocked with NADPH oxidase inhibitors, the toxicity was reduced by 15.4%. When prostaglandin production was blocked by cyclooxygenase inhibitors, the toxicity of the CM was reduced by 14.5%. When glutamate was removed by treatment with glutamate decarboxylase, the toxicity was reduced by 10.3%. When the inhibitors were added together to the astrocyte culture, the total toxicity of the CM was reduced by 91%. This was in reasonable agreement with the 85.37% total obtained by adding the individual components. The data show that activated astrocytes release a specific combination of neurotoxic compounds. They suggest that effective anti-inflammatory treatment of such neurodegenerative diseases as Alzheimer's disease, Parkinson's disease and Amyotrophic lateral sclerosis could be improved by using an appropriate combination of anti-inflammatory agents instead of relying on any single agent.</div></front></TEI><affiliations><list><country><li>Canada</li></country></list><tree><country name="Canada"><noRegion><name sortKey="Lee, M" sort="Lee, M" uniqKey="Lee M" first="M." last="Lee">M. Lee</name></noRegion><name sortKey="Mcgeer, E" sort="Mcgeer, E" uniqKey="Mcgeer E" first="E." last="Mcgeer">E. Mcgeer</name><name sortKey="Mcgeer, P L" sort="Mcgeer, P L" uniqKey="Mcgeer P" first="P. L." last="Mcgeer">P. L. Mcgeer</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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