Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

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"Köpfe" der aktuellen Meldungen:

Nina Höller

Nariae Baik-Schneditz

Bernhard Schwaberger

Lukas Peter Mileder

Niels Hammer

Daniel Scherr

Gerhard Pichler

Roland Malli

Gewählte Publikation:

SHR Neuro Krebs Kardio Lipid Stoffw Microb

Ho, JE; Chen, WY; Chen, MH; Larson, MG; McCabe, EL; Cheng, S; Ghorbani, A; Coglianese, E; Emilsson, V; Johnson, AD; Walter, S; Franceschini, N; O'Donnell, CJ; CARDIoGRAM Consortium; CHARGE Inflammation Working Group; Dehghan, A; Lu, C; Levy, D; Newton-Cheh, C; CHARGE Heart Failure Working Group; Lin, H; Felix, JF; Schreiter, ER; Vasan, RS; Januzzi, JL; Lee, RT; Wang, TJ; Assimes, TL; Deloukas, P; Erdmann, J; Holm, H; Kathiresan, S; König, IR; McPherson, R; Reilly, MP; Roberts, R; Samani, NJ; Schunkert, H; Stewart, AF.
Common genetic variation at the IL1RL1 locus regulates IL-33/ST2 signaling.
J Clin Invest. 2013; 123(10): 4208-4218. Doi: 10.1172/JCI67119 [OPEN ACCESS]
Web of Science PubMed FullText FullText_MUG

Study Group Mitglieder der Med Uni Graz:: Stojakovic Tatjana
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Abstract:: The suppression of tumorigenicity 2/IL-33 (ST2/IL-33) pathway has been implicated in several immune and inflammatory diseases. ST2 is produced as 2 isoforms. The membrane-bound isoform (ST2L) induces an immune response when bound to its ligand, IL-33. The other isoform is a soluble protein (sST2) that is thought to be a decoy receptor for IL-33 signaling. Elevated sST2 levels in serum are associated with an increased risk for cardiovascular disease. We investigated the determinants of sST2 plasma concentrations in 2,991 Framingham Offspring Cohort participants. While clinical and environmental factors explained some variation in sST2 levels, much of the variation in sST2 production was driven by genetic factors. In a genome-wide association study (GWAS), multiple SNPs within IL1RL1 (the gene encoding ST2) demonstrated associations with sST2 concentrations. Five missense variants of IL1RL1 correlated with higher sST2 levels in the GWAS and mapped to the intracellular domain of ST2, which is absent in sST2. In a cell culture model, IL1RL1 missense variants increased sST2 expression by inducing IL-33 expression and enhancing IL-33 responsiveness (via ST2L). Our data suggest that genetic variation in IL1RL1 can result in increased levels of sST2 and alter immune and inflammatory signaling through the ST2/IL-33 pathway.
Find related publications in this database (using NLM MeSH Indexing): Amino Acid Substitution -; Female -; Gene Expression -; Gene Expression Regulation -; Genetic Association Studies -; HEK293 Cells -; Humans -; Interleukins - genetics Interleukins - metabolism; Male -; Middle Aged -; Models, Molecular -; Myelin and Lymphocyte-Associated Proteolipid Proteins - metabolism; Myeloid Differentiation Factor 88 - metabolism; NF-kappa B - metabolism; Polymorphism, Single Nucleotide -; Promoter Regions, Genetic -; Prospective Studies -; Protein Structure, Tertiary -; Receptors, Cell Surface - chemistry Receptors, Cell Surface - genetics Receptors, Cell Surface - metabolism; Signal Transduction -; Transcription Factor AP-1 - metabolism