Reduced susceptibility to collagen-induced arthritis in DBA/1J mice expressing the TSG-6 transgene.
Arthritis Rheum
; 46(9): 2453-64, 2002 Sep.
Article
de En
| MEDLINE
| ID: mdl-12355494
ABSTRACT
OBJECTIVE:
Expression of TSG-6 (tumor necrosis factor-stimulated gene 6) is induced by proinflammatory cytokines. This study was undertaken to examine the effects of local expression of TSG-6 in arthritic joints of TSG-6 transgenic mice, in the collagen-induced arthritis (CIA) model.METHODS:
We generated transgenic mice that harbored the TSG-6 gene under the control of the T cell-specific lck promoter. Arthritis was induced by immunization with bovine type II collagen (CII), and its progression was monitored based on the incidence of arthritis, the arthritis index, and footpad swelling. Anti-CII antibodies and cytokine production were determined by enzyme-linked immunosorbent assay. Gene expression arrays were used to compare gene expression profiles of transgenic and control mice at various stages of CIA.RESULTS:
TSG-6 was expressed in limbs of transgenic mice after immunization with CII, while its expression in nontransgenic animals was insignificant. The incidence of CIA was reduced in TSG-6 transgenic animals, its onset delayed, and all parameters of clinical arthritis significantly reduced. However, the immune response against CII was not significantly inhibited in TSG-6 transgenic mice.CONCLUSION:
TSG-6 expression has been demonstrated in patients with rheumatoid and other forms of arthritis. Our data show that local expression of TSG-6 at sites of inflammation results in potent inhibition of inflammation and joint destruction in a model of autoimmune arthritis in mice. Therefore, it is likely that TSG-6 plays a similar modulatory role in human rheumatoid arthritis and related diseases and may have potential for the treatment of autoimmune arthritis in humans.
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Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Arthrite
/
Molécules d'adhérence cellulaire
/
Prédisposition génétique à une maladie
/
Collagène de type II
Type d'étude:
Prognostic_studies
Limites:
Animals
Langue:
En
Journal:
Arthritis Rheum
Année:
2002
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique