Artikel
Adipokines alter the interaction of rheumatoid arthritis synovial fibroblasts with endothelial cells
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Autoren
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Rebecca Hasseli
- Justus-Liebig Universität Gießen, Kerckhoff-Klinik GmbH, Rheumatologie u. klinische Immunologie, Osteologie, Physikalische Therapie, Bad Nauheim
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Klaus Frommer
- Justus-Liebig Universität Gießen, Kerckhoff-Klinik GmbH, Rheumatologie u. klinische Immunologie, Osteologie, Physikalische Therapie, Bad Nauheim
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Birgit Zimmermann
- Justus-Liebig Universität Gießen, Kerckhoff-Klinik GmbH, Rheumatologie u. klinische Immunologie, Osteologie, Physikalische Therapie, Bad Nauheim
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Stefan Rehart
- Agaplesion Markus Krankenhaus, Akademisches Lehrkrankenhaus der Johann Wolfgang Goethe-Universität, Klinik für Orthopädie und Unfallchirurgie, Frankfurt/Main
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Markus Schönburg
- Kerckhoff-Klinik, Gefäßchirurgie, Bad Nauheim
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Thomas Umscheid
- Helios William Harvey Klinik Bad Nauheim, Gefäßchirurgie, Bad Nauheim
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Ulf Müller-Ladner
- Justus-Liebig-Universität Gießen, Kerckhoff-Klinik GmbH, Rheumatologie u. klinische Immunologie, Osteologie, Physikalische Therapie, Bad Nauheim
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Elena Neumann
- Justus-Liebig-Universität Gießen, Kerckhoff-Klinik GmbH, Rheumatologie u. klinische Immunologie, Osteologie, Physikalische Therapie, Bad Nauheim
| Veröffentlicht: | 1. September 2015 |
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Gliederung
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Introduction: As an endocrine organ, adipose tissue plays a crucial role in inflammatory processes, which can be mediated by adipokines, important factors secreted by adipose tissue. We previously showed that within the murine organism rheumatoid arthritis (RA) synovial fibroblasts (SF) are able to migrate from one site to another. Due to this observation, the interaction between RASF and endothelial cells appears to be critical in this process.
Methods: RASF and EC were stimulated with the adipokines adiponectin (10 µg/ml), visfatin (100 ng/ml) and resistin (20 ng/ml), and “therapeutically” with methotrexate (MTX) (1.5 µM) and the glucocorticoids prednisolone (1 µM) and dexamethasone (1 µM). The expression of selected adhesion molecules from RASF and EC was analyzed by real-time PCR. RASF adhesion to EC was studied under static conditions using a cell-to-cell binding assay, while RASF adhesion to E-selectin was studied under flow conditions (flow rates: 18.4/30.5/60.5 ml/h) in a dynamic adhesion assay as flow conditions are required for selectins to be obtain their active conformation.
Results: Under static conditions, the adipokines caused an increased adhesion of RASF to EC (adiponectin: 37%, visfatin: 23%, resistin: 32%; n=6), while PNL and MTX caused a minor decrease (-7% for both; n=4). Dexamethasone did not change RASF adhesion to EC under static conditions. Under flow conditions, visfatin increased RASF adhesion to E-selectin (28%/87%/29%; n=3 for each flow rate), while dexamethasone decreased their adhesion ability (-33%/-35%/-41%; n=3 for each flow rate). mRNA expression of VCAM-1 in RASF (n=3) was reduced by stimulation with prednisolone (-3.3-fold) and dexamethasone ( 8.3 fold), respectively. TNF increased ICAM-1 mRNA expression (46.5 fold) and decreased P selectin mRNA expression (-7.7-fold) in EC (n=3).
Conclusion: Adipokines increase the cellular expression of adhesion molecules on RASF as well as EC and strengthen their interaction. This increased adhesion of RASF to endothelial cells mediated by adipokines could therefore influence the migration of RASF and thus the spreading of RA in vivo. As glucocorticoids and MTX antagonized these effects, our experiments can also explain some of the clinical effects observed in patients.
