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dc.contributor.authorHeymann, Michael C.
dc.contributor.authorWinkler, Stefan
dc.contributor.authorLuksch, Hella
dc.contributor.authorFlecks, Silvana
dc.contributor.authorFranke, Marcus
dc.contributor.authorRuss, Susanne
dc.contributor.authorOezen, Seza
dc.contributor.authorYilmaz, Engin
dc.contributor.authorKlein, Christoph
dc.contributor.authorKallinich, Tilmann
dc.contributor.authorLindemann, Dirk
dc.contributor.authorBrenner, Sebastian
dc.contributor.authorGanser, Gerd
dc.contributor.authorRoesler, Joachim
dc.contributor.authorRoesen-Wolff, Angela
dc.contributor.authorHofmann, Sigrun R.
dc.date.accessioned2019-12-10T10:38:42Z
dc.date.available2019-12-10T10:38:42Z
dc.date.issued2014
dc.identifier.issn0022-1767
dc.identifier.urihttps://doi.org/10.4049/jimmunol.1203524
dc.identifier.urihttp://hdl.handle.net/11655/14073
dc.description.abstractThe proinflammatory enzyme caspase-1 plays an important role in the innate immune system and is involved in a variety of inflammatory conditions. Rare naturally occurring human variants of the caspase-1 gene (CASP1) lead to different protein expression and structure and to decreased or absent enzymatic activity. Paradoxically, a significant number of patients with such variants suffer from febrile episodes despite decreased IL-1 beta production and secretion. In this study, we investigate how variant (pro) caspase-1 can possibly contribute to inflammation. In a transfection model, such variant procaspase-1 binds receptor interacting protein kinase 2 (RIP2) via Caspase activation and recruitment domain (CARD)/CARD interaction and thereby activates NF-kB, whereas wild-type procaspase-1 reduces intracellular RIP2 levels by enzymatic cleavage and release into the supernatant. We approach the protein interactions by coimmunoprecipitation and confocal microscopy and show that NF-kB activation is inhibited by anti-RIP2-short hairpin RNA and by the expression of a RIP2 CARD-only protein. In conclusion, variant procaspase-1 binds RIP2 and thereby activates NF-kB. This pathway could possibly contribute to proinflammatory signaling.
dc.language.isoen
dc.publisherAmer Assoc Immunologists
dc.relation.isversionof10.4049/jimmunol.1203524
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectImmunology
dc.titleHuman Procaspase-1 Variants With Decreased Enzymatic Activity Are Associated With Febrile Episodes And May Contribute To Inflammation Via Rip2 And Nf-Kb Signaling
dc.typeinfo:eu-repo/semantics/article
dc.typeinfo:eu-repo/semantics/publishedVersion
dc.relation.journalJournal Of Immunology
dc.contributor.departmentÇocuk Sağlığı ve Hastalıkları
dc.identifier.volume192
dc.identifier.issue9
dc.identifier.startpage4379
dc.identifier.endpage4385
dc.description.indexWoS
dc.description.indexScopus


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