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Specific Modulation of Astrocyte Inflammation by Inhibition of Mixed Lineage Kinases with CEP-1347

Specific Modulation of Astrocyte Inflammation by Inhibition of Mixed Lineage Kinases with CEP-1347

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FALSIG, Jeppe, Peter PÖRZGEN, Julie LOTHARIUS, Marcel LEIST, 2004. Specific Modulation of Astrocyte Inflammation by Inhibition of Mixed Lineage Kinases with CEP-1347. In: The Journal of Immunology. 173(4), pp. 2762-2770. ISSN 0022-1767. eISSN 1550-6606

@article{Falsig2004Speci-8605, title={Specific Modulation of Astrocyte Inflammation by Inhibition of Mixed Lineage Kinases with CEP-1347}, year={2004}, number={4}, volume={173}, issn={0022-1767}, journal={The Journal of Immunology}, pages={2762--2770}, author={Falsig, Jeppe and Pörzgen, Peter and Lotharius, Julie and Leist, Marcel} }

<rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bibo="http://purl.org/ontology/bibo/" xmlns:dspace="http://digital-repositories.org/ontologies/dspace/0.1.0#" xmlns:foaf="http://xmlns.com/foaf/0.1/" xmlns:void="http://rdfs.org/ns/void#" xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > <rdf:Description rdf:about="https://kops.uni-konstanz.de/rdf/resource/123456789/8605"> <dc:contributor>Falsig, Jeppe</dc:contributor> <dc:format>application/pdf</dc:format> <dspace:hasBitstream rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/8605/1/Jeppe_JI04.pdf"/> <dc:contributor>Leist, Marcel</dc:contributor> <foaf:homepage rdf:resource="http://localhost:8080/jspui"/> <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2011-03-24T17:45:02Z</dc:date> <dc:creator>Leist, Marcel</dc:creator> <dc:contributor>Pörzgen, Peter</dc:contributor> <dc:language>eng</dc:language> <dcterms:hasPart rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/8605/1/Jeppe_JI04.pdf"/> <dc:creator>Lotharius, Julie</dc:creator> <dc:creator>Pörzgen, Peter</dc:creator> <dcterms:bibliographicCitation>First publ. in: The Journal of Immunology ; 173 (2004), 5. - S. 2762-2770</dcterms:bibliographicCitation> <dc:rights>deposit-license</dc:rights> <dc:contributor>Lotharius, Julie</dc:contributor> <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/rdf/resource/123456789/28"/> <dcterms:abstract xml:lang="eng">Inflammatory conversion of murine astrocytes correlates with the activation of various MAPK, and inhibition of terminal MAPKs like JNK or p38 dampens the inflammatory reaction. Mixed lineage kinases (MLKs), a family of MAPK kinase kinases, may therefore be involved in astrocyte inflammation. In this study, we explored the effect of the MLK inhibitors CEP-1347 and CEP-11004 on the activation of murine astrocytes by either TNF plus IL-1 or by a complete cytokine mix containing additional IFN-{gamma}. The compounds blocked NO-, PG-, and IL-6 release with a median inhibitory concentration of ~100 nM. This activity correlated with a block of the JNK and the p38 pathways activated in complete cytokine mix-treated astrocytes. Although CEP-1347 did not affect the activation of NF-{kappa}B, it blocked the expression of cyclooxygenase-2 and inducible NO synthase at the transcriptional level. Quantitative transcript profiling of 17 inflammation-linked genes revealed a specific modulation pattern of astrocyte activation by MLK inhibition, for instance, characterized by up-regulation of the anti-stress factors inhibitor of apoptosis protein-2 and activated transcription factor 4, no effect on manganese superoxide dismutase and caspase-11, and down-regulation of major inflammatory players like TNF, GM-CSF, urokinase-type plasminogen activator, and IL-6. In conclusion, MLK inhibitors like CEP-1347 are highly potent astrocyte immune modulators with a novel spectrum of activity.</dcterms:abstract> <dcterms:issued>2004</dcterms:issued> <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/> <dcterms:title>Specific Modulation of Astrocyte Inflammation by Inhibition of Mixed Lineage Kinases with CEP-1347</dcterms:title> <dcterms:rights rdf:resource="http://nbn-resolving.org/urn:nbn:de:bsz:352-20140905103416863-3868037-7"/> <dc:creator>Falsig, Jeppe</dc:creator> <bibo:uri rdf:resource="http://kops.uni-konstanz.de/handle/123456789/8605"/> <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/rdf/resource/123456789/28"/> </rdf:Description> </rdf:RDF>

Dateiabrufe seit 01.10.2014 (Informationen über die Zugriffsstatistik)

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