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

Cytokine

Volumn 61, Issue 3, 2013, Pages 720-723

  Lamas, José Ramón ^a   Rodríguez Rodríguez, Luis ^a   Tornero Esteban, Pilar ^a   Villafuertes, Esther ^a   Hoyas, José ^a   Abasolo, Lydia ^a   Varadé, Jezabel ^a   Álvarez Lafuente, Roberto ^a   Urcelay, Elena ^a   Fernández Gutiérrez, Benjamín ^a  

^a HOSPITAL CLÍNICO SAN CARLOS   (Spain)

Author keywords

IL 6; Rheumatoid arthritis; SIL 6R; Single nucleotide polymorphism; TACE

Indexed keywords

INTERLEUKIN 6 RECEPTOR; METALLOPROTEINASE; PROTEIN ADAM17; UNCLASSIFIED DRUG;

ALTERNATIVE RNA SPLICING; ARTICLE; CONTROLLED STUDY; FEMALE; GENE EXPRESSION; GENE IDENTIFICATION; GENOTYPE; HUMAN; MAJOR CLINICAL STUDY; MALE; PRIORITY JOURNAL; PROTEIN BLOOD LEVEL; PROTEIN CLEAVAGE; PROTEIN DEGRADATION; PROTEIN DETERMINATION; PROTEIN EXPRESSION; PROTEIN PROTEIN INTERACTION; PROTEIN SYNTHESIS; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; RHEUMATOID ARTHRITIS; SINGLE NUCLEOTIDE POLYMORPHISM; SOLUBLE IL 6R GENE;

ADAM PROTEINS; ADOLESCENT; ADULT; AGED; ALTERNATIVE SPLICING; ARTHRITIS, RHEUMATOID; DEMOGRAPHY; FEMALE; GENE EXPRESSION REGULATION; GENETIC PREDISPOSITION TO DISEASE; HUMANS; MALE; MIDDLE AGED; POLYMORPHISM, SINGLE NUCLEOTIDE; PROTEOLYSIS; RECEPTORS, INTERLEUKIN-6; SOLUBILITY; YOUNG ADULT;

EID: 84875381278     PISSN: 10434666     EISSN: 10960023     Source Type: Journal    
DOI: 10.1016/j.cyto.2012.12.025     Document Type: Article

References (16)

1. Dayer J.M., Choy E. Therapeutic targets in rheumatoid arthritis: the interleukin-6 receptor. Rheumatology (Oxford) 2010, 49:15-24.
2. Jones S.A., Rose-John S. The role of soluble receptors in cytokine biology: the agonistic properties of the sIL-6R/IL-6 complex. Biochim Biophys Acta 2002, 1592:251-263.
3. Rose-John S., Scheller J., Elson G., et al. Interleukin-6 biology is coordinated by membrane-bound and soluble receptors. J Leukoc Biol 2006, 80:227-236.
4. Kim L.H., Lee H.S., Kim Y.J., et al. Identification of novel SNPs in the interleukin 6 receptor gene (IL6R). Hum Mutat 2003, 21:450-451.
5. Mullberg J., Oberthur W., Lottspeich F., et al. The soluble human IL-6 receptor. Mutational characterization of the proteolytic cleavage site. J Immunol 1994, 152:4958-4968.
6. Galicia J.C., Tai H., Komatsu Y., et al. Polymorphisms in the IL-6 receptor (IL-6R) gene: strong evidence that serum levels of soluble IL-6R are genetically influenced. Genes Immun 2004, 5:513-516.
7. Marinou I., Walters K., Winfield J., et al. A gain of function polymorphism in the interleukin 6 receptor influences RA susceptibility. Ann Rheum Dis 2010, 69:1191-1194.
8. Zhang S., Zhang P., Huang Q.Y. Association of the D358A polymorphism of IL6R gene with type 2 diabetes in Hubei Han Chinese. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2009, 26:452-456.
9. Hassan B., Maxwell J.R., Hyrich K.L., et al. Genotype at the sIL-6R A358C polymorphism does not influence response to anti-TNF therapy in patients with rheumatoid arthritis. Rheumatology (Oxford) 2010, 49:43-47.
10. Rodriguez-Rodriguez L., Lamas J.R., Varade J., et al. Plasma soluble IL-6 receptor concentration in rheumatoid arthritis: associations with the rs8192284 IL6R polymorphism and with disease activity. Rheumatol Int 2011, 31:409-413.
11. Chalaris A., Rabe B., Paliga K., et al. Apoptosis is a natural stimulus of IL6R shedding and contributes to the proinflammatory trans-signaling function of neutrophils. Blood 2007, 110:1748-1755.
12. Lemmers A., Gustot T., Durnez A., et al. An inhibitor of interleukin-6 trans-signalling, sgp130, contributes to impaired acute phase response in human chronic liver disease. Clin Exp Immunol 2009, 156:518-527.
13. Lamas J.R., Rodriguez-Rodriguez L., Varade J., et al. Influence of IL6R rs8192284 polymorphism status in disease activity in rheumatoid arthritis. J Rheumatol 2010, 37:1579-1581.
14. Desgeorges A., Gabay C., Silacci P., et al. Concentrations and origins of soluble interleukin 6 receptor-alpha in serum and synovial fluid. J Rheumatol 1997, 24:1510-1516.
15. Briso E.M., Dienz O., Rincon M. Cutting edge: soluble IL-6R is produced by IL-6R ectodomain shedding in activated CD4 T cells. J Immunol 2008, 180:7102-7106.
16. Franchimont N., Lambert C., Huynen P., et al. Interleukin-6 receptor shedding is enhanced by interleukin-1beta and tumor necrosis factor alpha and is partially mediated by tumor necrosis factor alpha-converting enzyme in osteoblast-like cells. Arthritis Rheum 2005, 52:84-93.