Monocytes are essential for inhibition of synovial T-cell glucocorticoid-mediated apoptosis in rheumatoid arthritis.
Arthritis Res Ther
; 10(6): R147, 2008.
Article
em En
| MEDLINE
| ID: mdl-19099567
ABSTRACT
INTRODUCTION:
Rheumatoid arthritis (RA) is characterized by synovial inflammation with local accumulation of mononuclear cells such as macrophages and lymphocytes. We previously demonstrated that intra-articular glucocorticoids decrease the synovial tissue (ST) T-cell population and therefore aimed to investigate whether this is mediated through modulation of apoptosis.METHODS:
Apoptosis and cell phenotype were evaluated by immunohistochemistry and dual-immunofluorescence in synovial biopsy sections from 12 RA patients before and after a mean of 11 days of an intra-articular triamcinolone knee injection. In vitro, RA synovial fluid (SF)-derived T cells were evaluated for Annexin V expression by multicolor flow cytometry after 24-hour exposure to dexamethasone, methylprednisolone, or triamcinolone. We also tested induction of apoptosis by dexamethasone on psoriatic arthritis SF-derived T cells using the same method.RESULTS:
Intra-articular glucocorticoids reduced ST T cells but not macrophage number. ST apoptosis levels were unchanged following treatment, virtually absent from lymphoid aggregates, and minimal in CD3+ cells both before and after treatment. RA SF T cells were resistant to glucocorticoid-induced apoptosis when cultured in the presence of monocytes but were rendered sensitive to all three tested compounds upon SF isolation. Furthermore, transwell coculture of monocytes and T cells demonstrated that soluble factor(s) and not cellular contact are essential for T-cell resistance to glucocorticoid-mediated apoptosis. This feature is RA-specific as far as dexamethasone-induced apoptosis in nonisolated SF T cells obtained from psoriatic arthritis patients is concerned.CONCLUSIONS:
We demonstrate that monocytes rescue synovial T cells from glucocorticoid-induced apoptosis, a feature that is specific for RA. To overcome this, we propose the use of monocyte-targeted therapies rather than T-cell apoptosis-inducing therapies.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Artrite Reumatoide
/
Líquido Sinovial
/
Monócitos
/
Linfócitos T
/
Apoptose
/
Glucocorticoides
Limite:
Adult
/
Aged
/
Aged80
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Arthritis Res Ther
Assunto da revista:
REUMATOLOGIA
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Suécia