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Prevention of experimental colitis by a selective inhibitor of the immunoproteasome

Prevention of experimental colitis by a selective inhibitor of the immunoproteasome


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BASLER, Michael, Maya DAJEE, Carlo MOLL, Marcus GRÖTTRUP, Christopher J. KIRK, 2010. Prevention of experimental colitis by a selective inhibitor of the immunoproteasome. In: The Journal of Immunology. 185(1), pp. 634-641. ISSN 0022-1767. eISSN 1550-6606

@article{Basler2010-07-01Preve-14968, title={Prevention of experimental colitis by a selective inhibitor of the immunoproteasome}, year={2010}, doi={10.4049/jimmunol.0903182}, number={1}, volume={185}, issn={0022-1767}, journal={The Journal of Immunology}, pages={634--641}, author={Basler, Michael and Dajee, Maya and Moll, Carlo and Gröttrup, Marcus and Kirk, Christopher J.} }

<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/123456789/14968"> <dc:contributor>Moll, Carlo</dc:contributor> <dc:creator>Dajee, Maya</dc:creator> <dc:contributor>Gröttrup, Marcus</dc:contributor> <dc:rights>deposit-license</dc:rights> <dc:contributor>Basler, Michael</dc:contributor> <dc:creator>Moll, Carlo</dc:creator> <dcterms:abstract xml:lang="eng">The proteasome, a multicatalytic protease, is responsible for the degradation of intracellular proteins. Stimulation of cells with inflammatory cytokines, such as IFN-γ, leads to the replacement of the constitutive catalytic proteasome subunits by the inducible subunits low molecular mass polypeptide (LMP)2 (β1i), multicatalytic endopeptidase complex-like-1 (β2i), and LMP7 (β5i), which are required for the production of certain MHC class I-restricted T cell epitopes. In this study, we investigated the effect of immunoproteasomes on the development of dextran sulfate sodium-induced colitis. Colitis induction in LMP2-, LMP7-, and multicatalytic endopeptidase complex-like-1–deficient mice caused reduced weight loss compared with wild-type mice. Although colon lengths were shortened in wild-type mice, no reduction was observed in immunoproteasome-deficient mice. In accordance with this, proinflammatory cytokines, such as TNF-α and IL-1β, were not upregulated in these mice. Blockage of LMP7 by a novel LMP7-selective inhibitor (PR-957) strongly reduced pathological symptoms of dextran sulfate sodium-induced colitis. Production of numerous cytokines in PR-957–treated mice was suppressed, resulting in reduced inflammation and tissue destruction. Taken together, these results demonstrate that an immunoproteasome-specific inhibitor can be used to attenuate autoimmune diseases like colitis.</dcterms:abstract> <dc:contributor>Dajee, Maya</dc:contributor> <dc:creator>Gröttrup, Marcus</dc:creator> <dcterms:title>Prevention of experimental colitis by a selective inhibitor of the immunoproteasome</dcterms:title> <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2011-08-18T15:53:56Z</dcterms:available> <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2011-08-18T15:53:56Z</dc:date> <dcterms:rights rdf:resource="http://nbn-resolving.org/urn:nbn:de:bsz:352-20140905103605204-4002607-1"/> <dcterms:issued>2010-07-01</dcterms:issued> <dc:contributor>Kirk, Christopher J.</dc:contributor> <bibo:uri rdf:resource="http://kops.uni-konstanz.de/handle/123456789/14968"/> <dc:creator>Basler, Michael</dc:creator> <dc:language>eng</dc:language> <dcterms:bibliographicCitation>Publ. in: The Journal of Immunology ; 185 (2010), 1. - pp. 634-641</dcterms:bibliographicCitation> <dc:creator>Kirk, Christopher J.</dc:creator> </rdf:Description> </rdf:RDF>

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