title: Alternative splicing and proteolytic rupture contribute to the generation of soluble IL-6 receptors (sIL-6R) in rheumatoid arthritis.
abstract: OBJECTIVE
  To describe the relationship between the two mechanisms involved in sIL6R generation in rheumatoid arthritis (RA).
  
  
  METHODS
  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.
  
  
  RESULTS
  Increased sIL-6R plasma levels and expression of spliced isoform generating sIL-6R are genotype dependent. ADAM17 concentrations were independent of the genotype studied.
  
  
  CONCLUSIONS
  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.
authors: UGC de Reumatología, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos, Madrid, Spain. jrlamas@gmail.com
authors: José Ramón
authors: JR
authors: Lamas
authors: Luis
authors: L
authors: Rodríguez-Rodríguez
authors: Pilar
authors: P
authors: Tornero-Esteban
authors: Esther
authors: E
authors: Villafuertes
authors: José
authors: J
authors: Hoyas
authors: Lydia
authors: L
authors: Abasolo
authors: Jezabel
authors: J
authors: Varadé
authors: Roberto
authors: R
authors: Alvarez-Lafuente
authors: Elena
authors: E
authors: Urcelay
authors: Benjamín
authors: B
authors: Fernández-Gutiérrez
mesh_terms: D051722:ADAM Proteins / Q000097:blood / Q000235:genetics; D000072198:ADAM17 Protein; D000293:Adolescent; D000328:Adult; D000368:Aged; D017398:Alternative Splicing / Q000235:genetics*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000235:genetics*; D003710:Demography; D005260:Female; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D059748:Proteolysis; D019947:Receptors, Interleukin-6 / Q000097:blood / Q000235:genetics*; D012995:Solubility; D055815:Young Adult
chemical_list: D019947:Receptors, Interleukin-6; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human