Alternative splicing and proteolytic rupture contribute to the generation of soluble IL-6 receptors (sIL-6R) in rheumatoid arthritis

Cytokine. 2013 Mar;61(3):720-3. doi: 10.1016/j.cyto.2012.12.025. Epub 2013 Jan 29.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAM Proteins / blood
  • ADAM Proteins / genetics
  • ADAM17 Protein
  • Adolescent
  • Adult
  • Aged
  • Alternative Splicing / genetics*
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / genetics*
  • Demography
  • Female
  • Gene Expression Regulation
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics
  • Proteolysis*
  • Receptors, Interleukin-6 / blood
  • Receptors, Interleukin-6 / genetics*
  • Solubility
  • Young Adult

Substances

  • Receptors, Interleukin-6
  • ADAM Proteins
  • ADAM17 Protein
  • ADAM17 protein, human