Lowin, Torsten and Straub, Rainer H. and Neumann, Elena and Bosserhoff, Anja and Vogel, Corinna and Moissl, Christine and Anders, Sven and Mueller-Ladner, Ulf and Schedel, Joerg (2009) Glucocorticoids Increase alpha 5 Integrin Expression and Adhesion of Synovial Fibroblasts but Inhibit ERK Signaling, Migration, and Cartilage Invasion. ARTHRITIS AND RHEUMATISM, 60 (12). pp. 3623-3632. ISSN 0004-3591, 1529-0131
Full text not available from this repository. (Request a copy)Abstract
Objective. 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 alpha 5, alpha v, and beta 1 was higher at the site of invasion compared with the sublining zone. Testosterone and 17 beta-estradiol had no influence on integrin levels, but cortisol up-regulated expression of the alpha 5 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 alpha 5 integrin increased SF migration, indicating that up-regulated alpha 5 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 alpha 5 integrin.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TUMOR-NECROSIS-FACTOR; BREAST-CANCER CELLS; RHEUMATOID-ARTHRITIS; IN-VITRO; GENE-EXPRESSION; GROWTH-FACTOR; MATRIX PROTEINS; JNK PATHWAY; LUNG-CANCER; DEXAMETHASONE; |
| Subjects: | 500 Science > 570 Life sciences 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I Medicine > Lehrstuhl für Pathologie Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie > Lehrstuhl für Mikrobiologie (Archaeenzentrum) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 27 Aug 2020 10:54 |
| Last Modified: | 27 Aug 2020 10:54 |
| URI: | https://pred.uni-regensburg.de/id/eprint/27998 |
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