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A selective inhibitor of the immunoproteasome subunit LMP7 blocks cytokine production and attenuates progression of experimental arthritis

A selective inhibitor of the immunoproteasome subunit LMP7 blocks cytokine production and attenuates progression of experimental arthritis

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MUCHAMUEL, Tony, Michael BASLER, Monette A. AUJAY, Erika SUZUKI, Khalid W. KALIM, Christoph LAUER, Catherine SYLVAIN, Eileen R. RING, Jamie SHIELDS, Jing JIANG, Peter SHWONEK, Francesco PARLATI, Susan D. DEMO, Mark K. BENNETT, Christopher J. KIRK, Marcus GROETTRUP, 2009. A selective inhibitor of the immunoproteasome subunit LMP7 blocks cytokine production and attenuates progression of experimental arthritis. In: Nature Medicine. 15(7), pp. 781-787. ISSN 1078-8956. eISSN 1546-170X

@article{Muchamuel2009selec-1148, title={A selective inhibitor of the immunoproteasome subunit LMP7 blocks cytokine production and attenuates progression of experimental arthritis}, year={2009}, doi={10.1038/nm.1978}, number={7}, volume={15}, issn={1078-8956}, journal={Nature Medicine}, pages={781--787}, author={Muchamuel, Tony and Basler, Michael and Aujay, Monette A. and Suzuki, Erika and Kalim, Khalid W. and Lauer, Christoph and Sylvain, Catherine and Ring, Eileen R. and Shields, Jamie and Jiang, Jing and Shwonek, Peter and Parlati, Francesco and Demo, Susan D. and Bennett, Mark K. and Kirk, Christopher J. and Groettrup, Marcus} }

<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bibo="http://purl.org/ontology/bibo/" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > <rdf:Description rdf:about="https://kops.uni-konstanz.de/rdf/resource/123456789/1148"> <dc:creator>Basler, Michael</dc:creator> <dcterms:title>A selective inhibitor of the immunoproteasome subunit LMP7 blocks cytokine production and attenuates progression of experimental arthritis</dcterms:title> <dc:contributor>Aujay, Monette A.</dc:contributor> <dc:contributor>Demo, Susan D.</dc:contributor> <dc:creator>Parlati, Francesco</dc:creator> <dc:creator>Shields, Jamie</dc:creator> <dcterms:bibliographicCitation>Publ. in: Nature Medicine 15 (2009), 7, pp. 781-787</dcterms:bibliographicCitation> <dc:contributor>Kalim, Khalid W.</dc:contributor> <dc:contributor>Basler, Michael</dc:contributor> <dc:rights>deposit-license</dc:rights> <dc:contributor>Shields, Jamie</dc:contributor> <dc:contributor>Parlati, Francesco</dc:contributor> <dc:contributor>Groettrup, Marcus</dc:contributor> <dc:contributor>Jiang, Jing</dc:contributor> <dc:creator>Suzuki, Erika</dc:creator> <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2011-03-23T09:06:28Z</dcterms:available> <dc:creator>Groettrup, Marcus</dc:creator> <dc:creator>Jiang, Jing</dc:creator> <dc:creator>Shwonek, Peter</dc:creator> <bibo:uri rdf:resource="http://kops.uni-konstanz.de/handle/123456789/1148"/> <dcterms:rights rdf:resource="http://nbn-resolving.org/urn:nbn:de:bsz:352-20140905103416863-3868037-7"/> <dc:creator>Bennett, Mark K.</dc:creator> <dc:creator>Kalim, Khalid W.</dc:creator> <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2011-03-23T09:06:28Z</dc:date> <dc:creator>Demo, Susan D.</dc:creator> <dc:contributor>Sylvain, Catherine</dc:contributor> <dc:creator>Ring, Eileen R.</dc:creator> <dc:contributor>Muchamuel, Tony</dc:contributor> <dc:creator>Kirk, Christopher J.</dc:creator> <dc:creator>Aujay, Monette A.</dc:creator> <dc:contributor>Ring, Eileen R.</dc:contributor> <dcterms:issued>2009</dcterms:issued> <dc:contributor>Suzuki, Erika</dc:contributor> <dc:creator>Lauer, Christoph</dc:creator> <dc:creator>Muchamuel, Tony</dc:creator> <dcterms:abstract xml:lang="eng">The immunoproteasome, a distinct class of proteasome found predominantly in monocytes and lymphocytes, is known to shape the antigenic repertoire presented on class I major histocompatibility complexes (MHC-I). However, a specific role for the immunoproteasome in regulating other facets of immune responses has not been established. We describe here the characterization of PR-957, a selective inhibitor of low-molecular mass polypeptide-7 (LMP7, encoded by Psmb8), the chymotrypsin-like subunit of the immunoproteasome. PR-957 blocked presentation of LMP7-specific, MHC-I-restricted antigens in vitro and in vivo. Selective inhibition of LMP7 by PR-957 blocked production of interleukin-23 (IL-23) by activated monocytes and interferon-gamma and IL-2 by T cells. In mouse models of rheumatoid arthritis, PR-957 treatment reversed signs of disease and resulted in reductions in cellular infiltration, cytokine production and autoantibody levels. These studies reveal a unique role for LMP7 in controlling pathogenic immune responses and provide a therapeutic rationale for targeting LMP7 in autoimmune disorders.</dcterms:abstract> <dc:contributor>Bennett, Mark K.</dc:contributor> <dc:contributor>Kirk, Christopher J.</dc:contributor> <dc:language>eng</dc:language> <dc:contributor>Lauer, Christoph</dc:contributor> <dc:contributor>Shwonek, Peter</dc:contributor> <dc:creator>Sylvain, Catherine</dc:creator> </rdf:Description> </rdf:RDF>

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