In:
Arthritis & Rheumatism, Wiley, Vol. 60, No. 12 ( 2009-12), p. 3623-3632
Abstract:
In rheumatoid arthritis (RA), integrins mediate cell adhesion, migration, and invasion, and their expression is regulated by cytokines and growth factors. The aim of this study was to investigate whether hormones such as cortisol or other steroids can influence integrin expression and function in the synovial cells of patients with RA. Methods We performed immunofluorescence and fluorescence‐activated cell sorting analyses to quantify surface integrin levels. Adhesion and migration assays were performed to study the function of synovial fibroblasts (SFs). ERK activation was measured by cellular activation of a signaling enzyme‐linked immunosorbent assay. Invasion of SFs into cartilage was determined in the SCID mouse coimplantation model of RA in vivo. Results In RA, expression of integrin subunits α5, αv, and β1 was higher at the site of invasion compared with the sublining zone. Testosterone and 17β‐estradiol had no influence on integrin levels, but cortisol up‐regulated expression of the α5 subunit in a time‐dependent and dose‐dependent manner. In addition, cortisol increased the adhesion of SFs to fibronectin and inhibited ERK signaling upon integrin activation or upon stimulation with tumor necrosis factor. Small interfering RNA or a neutralizing antibody to α5 integrin increased SF migration, indicating that up‐regulated α5 integrin is responsible for an immobile phenotype. In addition, in the SCID mouse model, SF invasion into cartilage was attenuated by glucocorticoid treatment in vivo. Conclusion Glucocorticoids increase integrin expression and the adhesion of cells to fibronectin, inhibit ERK signaling, and down‐regulate the invasiveness of SFs in vivo. This study demonstrates that an important antiinflammatory aspect of glucocorticoids is regulating the expression and function of α5 integrin.
Type of Medium:
Online Resource
ISSN:
0004-3591
,
1529-0131
Language:
English
Publisher:
Wiley
Publication Date:
2009
detail.hit.zdb_id:
2014367-9
detail.hit.zdb_id:
127294-9
