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). 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.

journal_name

Cytokine

journal_title

Cytokine

authors

Lamas JR,Rodríguez-Rodríguez L,Tornero-Esteban P,Villafuertes E,Hoyas J,Abasolo L,Varadé J,Alvarez-Lafuente R,Urcelay E,Fernández-Gutiérrez B

doi

10.1016/j.cyto.2012.12.025

subject

Has Abstract

pub_date

2013-03-01 00:00:00

pages

720-3

issue

3

eissn

1043-4666

issn

1096-0023

pii

S1043-4666(13)00004-5

journal_volume

61

pub_type

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