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Cyclosporin A prevents the histologic damage of antigen arthritis without inducing fibrosis
M J Benito1, O Sánchez-Pernaute, M J López-Armada
1Fundación Jiménez Díaz, and Universidad Autónoma, Madrid, Spain.
Objective:
To study the effects of cyclosporin A (CSA) in a model of rheumatoid arthritis (RA) and the activation of growth factors related to pannus development at the site of injury.
Methods:
Antigen arthritis was induced in the knees of 14 New Zealand rabbits, and the animals were randomized into 2 therapeutic groups: CSA at 10 mg/kg/day and CSA solvent. After 3 weeks of treatment, the rabbits were killed, and synovial tissues were obtained and compared with healthy specimens with regard to histopathologic lesions, deposition of transforming growth factor beta (TGFbeta) and collagens, and messenger RNA expression of platelet-derived growth factor B (PDGF-B) and TGFbeta. The effect of CSA on the expression of TGFbeta and PDGF-B was also examined in cultured synovial cells.
Results:
CSA administration alleviated the histologic damage and avoided the overdeposition of matrix elements in the injured tissue. It was also able to normalize the enhanced expression of TGFbeta and PDGF-B observed in the untreated rabbits. Despite this modulation found in vivo, CSA up-regulated in a dose-dependent manner the gene expression of both trophic factors by healthy cultured synovial cells.
Conclusion:
The present study shows that continuous administration of CSA prevents the development of chronic synovitis in an experimental model of RA. As reported in other cell types, CSA promoted TGFbeta transcription by synovial cells in vitro, but failed to display a profibrogenic effect in the inflamed environment.
Insights
Cyclosporin A (CSA) prevents chronic synovitis in rheumatoid arthritis (RA) models by reducing tissue damage and normalizing growth factor expression. However, CSA also increases growth factor gene expression in healthy synovial cells in vitro.
Area of Science:
- Immunology
- Rheumatology
- Cell Biology
Background:
- Rheumatoid arthritis (RA) involves chronic synovitis and pannus development.
- Growth factors like TGF-beta and PDGF-B are implicated in RA pathogenesis.
- Cyclosporin A (CSA) is an immunosuppressant with potential anti-inflammatory effects.
Purpose of the Study:
- To investigate the effects of CSA on a rabbit model of RA.
- To assess CSA's impact on growth factor activation and pannus development.
- To examine CSA's influence on synovial cell gene expression.
Main Methods:
- Induced antigen arthritis in rabbit knees, treated with CSA or solvent.
- Analyzed synovial tissues for histopathology, collagen, TGF-beta, and PDGF-B mRNA.
- Examined CSA's effect on TGF-beta and PDGF-B expression in cultured synovial cells.
Main Results:
- CSA treatment reduced histologic damage and matrix deposition in vivo.
- CSA normalized elevated TGF-beta and PDGF-B expression in treated rabbits.
- CSA dose-dependently upregulated TGF-beta and PDGF-B gene expression in healthy cultured synovial cells.
Conclusions:
- Continuous CSA administration prevents chronic synovitis in experimental RA.
- CSA modulates growth factor expression in vivo but upregulates it in vitro.
- CSA's profibrogenic effect was not observed in the inflamed RA environment.