Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Hermann, J; Gruber, S; Neufeld, JB; Grundtner, P; Graninger, M; Graninger, WB; Berghold, A; Gasche, C.
IL10R1 loss-of-function alleles in rheumatoid arthritis and systemic lupus erythematosus.
Clin Exp Rheumatol. 2009; 27(4):603-608
Web of Science
PubMed
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- Führende Autor*innen der Med Uni Graz
- Hermann Josef
- Co-Autor*innen der Med Uni Graz
- Berghold Andrea
- Graninger Monika
- Graninger Winfried
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- Abstract:
- IL-10 is a pleiotropic cytokine involved in the regulation of innate and cell-mediated immunity and a key mediator within the disturbed SLE immune system. IL-10 binds to IL10R1, which is expressed on a variety of immune cells and activates the JAK-STAT pathway. Two (out of several known) genetic IL10R1 variants may alter IL-10 binding or signal transduction. Here we investigate the differential activity of these IL10R1 variants and their possible association with RA or SLE susceptibility. IL10R1-wt, IL10R1-S138G, IL10R1-G330R, or IL10R1- S138G +G330R were cloned into pIRESpuro3 and transfected into HeLa cells. Single cell clones were tested for IL-10-induced SOCS3- and SLAM gene expression by real-time PCR. DNA from 182 RA patients, 222 SLE patients, and 250 healthy controls was genotyped by allele-specific PCR. A biphasic increase of SOCS3 mRNA was observed that peaked at 15 minutes and 4 hours after IL-10 stimulation. The presence of IL10R1 S138G and G330R showed a weaker induction of both SOCS3 and SLAM upon stimulation with IL-10. In RA a homozygous G330R genotype was more commonly present than in controls (15.4% vs. 7.6%; p<0.05). In SLE the G330R allele frequency was also increased (36.3% vs. 30.0%; p<0.05) without showing a gene-dose relationship at the genotype level. Based on these results, both variants of the IL10R1 gene are loss-of-function alleles. IL10R1 G330R may possibly contribute to RA or SLE disease susceptibility in Caucasian populations.
- Find related publications in this database (using NLM MeSH Indexing)
- Antigens, CD - genetics
- Antigens, CD - metabolism
- Arthritis, Rheumatoid - genetics
- Arthritis, Rheumatoid - immunology
- Clone Cells -
- Female -
- Gene Expression -
- Gene Silencing -
- Genetic Predisposition to Disease -
- HeLa Cells -
- Humans -
- Interleukin-10 - genetics
- Lupus Erythematosus, Systemic - genetics
- Lupus Erythematosus, Systemic - immunology
- Male -
- Middle Aged -
- Polymorphism, Single Nucleotide -
- Receptors, Cell Surface - genetics
- Receptors, Cell Surface - metabolism
- Signaling Lymphocytic Activation Molecule Family Member 1 -
- Suppressor of Cytokine Signaling 3 Protein -
- Suppressor of Cytokine Signaling Proteins - genetics
- Suppressor of Cytokine Signaling Proteins - metabolism
- Transfection -
- Find related publications in this database (Keywords)
- Rheumatoid arthritis
- systemic lupus erythematosus
- single nucleotide polymorphism
- interleukin-10 receptor
- IL10R1