Functional characterization of a soluble gp130 isoform and its therapeutic capacity in an experimental model of inflammatory arthritis.
Arthritis Rheum
; 54(5): 1662-72, 2006 May.
Article
en En
| MEDLINE
| ID: mdl-16646038
ABSTRACT
OBJECTIVE:
Soluble gp130 is the naturally occurring antagonist of the interleukin-6 (IL-6)/soluble IL-6 receptor (sIL-6R) complex and selectively inhibits IL-6 trans-signaling. Several isoforms of soluble gp130 have been identified, including an autoantigenic form termed gp130-RAPS (for gp130 of the rheumatoid arthritis antigenic peptide-bearing soluble form) that is present in the serum and synovial fluid of patients with rheumatoid arthritis. The aim of this study was to evaluate the functional properties of gp130-RAPS.METHODS:
To define a role for gp130-RAPS in arthritis, a recombinant version was generated using a baculovirus expression system, and its activities were tested in vitro and in vivo.RESULTS:
Gp130-RAPS was shown to bind with high affinity to the stable IL-6/sIL-6R complex, hyper-IL-6, and to effectively modulate leukocyte migration in murine acute peritonitis. A single intraarticular injection of gp130-RAPS suppressed chronic antigen-induced arthritis in association with a reduction in local activation of signal transducer and activator of transcription 3. Although gp130-RAPS contains the previously identified autoantigenic sequence Asn-Ile-Ala-Ser-Phe (NIASF), no increase in the prevalence of anti- gp130-RAPS antibodies was observed in serum or synovial fluid obtained from patients with rheumatoid arthritis.CONCLUSION:
The use of inhibitory antibodies to block IL-6 responses has shown considerable clinical promise. However, the results presented herein suggest that selective targeting of IL-6 trans-signaling may represent a viable alternative to this strategy. In this respect, our present results suggest that the soluble gp130 isoform gp130-RAPS may be useful in the treatment of chronic inflammatory arthritis.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Artritis
/
Receptor gp130 de Citocinas
Tipo de estudio:
Risk_factors_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Arthritis Rheum
Año:
2006
Tipo del documento:
Article
País de afiliación:
Reino Unido