Alternative splicing and proteolytic rupture contribute to the generation of soluble IL-6 receptors (sIL-6R) in rheumatoid arthritis
Autor: | José Ramón Lamas, Jezabel Varadé, Elena Urcelay, Lydia Abasolo, Luis Rodriguez-Rodriguez, J. Hoyas, E. Villafuertes, P. Tornero-Esteban, Roberto Alvarez-Lafuente, Benjamín Fernández-Gutiérrez |
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Rok vydání: | 2013 |
Předmět: |
Adult
Male musculoskeletal diseases Gene isoform Adolescent medicine.medical_treatment Immunology Single-nucleotide polymorphism ADAM17 Protein Polymorphism Single Nucleotide Biochemistry Arthritis Rheumatoid Young Adult Genotype medicine Humans Immunology and Allergy Genetic Predisposition to Disease Receptor Interleukin 6 Molecular Biology Aged Demography Protease biology Chemistry Alternative splicing Hematology Middle Aged medicine.disease Receptors Interleukin-6 Molecular biology ADAM Proteins Alternative Splicing Gene Expression Regulation Solubility Rheumatoid arthritis Proteolysis biology.protein Female |
Zdroj: | Cytokine. 61:720-723 |
ISSN: | 1043-4666 |
Popis: | Objective To describe the relationship between the two mechanisms involved in sIL6R generation in rheumatoid arthritis (RA). Method RA patients were selected from a group of subjects genotyped for the rs8192284 SNP, located at the proteolytic cleavage site of IL-6R. sIL6R and protease levels (ADAM17) were measured and the contribution of alternative splicing in the generation of sIL-6R was evaluated through qRT-PCR. Result Increased sIL-6R plasma levels and expression of spliced isoform generating sIL-6R are genotype dependent. ADAM17 concentrations were independent of the genotype studied. Conclusion Alternative splicing and proteolytic cleavage participate in sIL-6R generation in RA. The rs8192284 polymorphism determines the sIL-6R plasma level through differential proteolytic rupture controlled by ADAM17. |
Databáze: | OpenAIRE |
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