NDLI: Human procaspase-1 variants with decreased enzymatic activity are associated with febrile episodes and may contribute to inflammation via RIP2 and NF-κB signaling.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Ganser, Gerd Hofmann, Sigrun R. Rösen-Wolff, Angela Kallinich, Tilmann Brenner, Sebastian Ozen, Seza Heymann, Michael C. Yilmaz, Engin Klein, Christoph Luksch, Hella Flecks, Silvana Ruß, Susanne Lindemann, Dirk Franke, Marcus Roesler, Joachim Winkler, Stefan
Description	Author Affiliation: Heymann MC ( Klinik und Poliklinik für Kinder- und Jugendmedizin, Medizinische Fakultät der Technischen Universität Dresden, 01307 Dresden, Germany)
Abstract	The 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-1ß 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-κB, 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-κB 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-κB. This pathway could possibly contribute to proinflammatory signaling.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	9
Volume Number	192
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2014-05-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Caspase 1 Genetics Fever Inflammation Nf-kappa B Metabolism Receptor-interacting Protein Serine-threonine Kinase 2 Blotting, Western Enzymology Fluorescent Antibody Technique Gene Knockdown Techniques Genetic Variation Hek293 Cells Immunoprecipitation Immunology Signal Transduction Physiology Transduction, Genetic Transfection Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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