Date: Sunday, November 8, 2015
Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Rheumatoid Arthritis (RA) is a systemic chronic inflammatory disease. Adipose tissue, being an endocrine organ, plays an important role in inflammatory processes. Adipokines are immunomodulatory factors mainly secreted by the adipose tissue. In previous studies we could show that RA synovial fibroblasts (SF) are able to migrate long distances in vivo via the vasculature. Therefore, we analysed the role of adipokines on RASF and endothelial cell (EC) adhesion and interaction. Static and dynamic adhesion as well as the expression of selected adhesion molecules on RASF and EC after stimulation with adipokines (adiponectin, visfatin, resistin), glucocorticoids and methotrexate (MTX) were evaluated.
Primary RASF and EC were stimulated with adiponectin (10 µg/ml), visfatin (100 ng/ml) and resistin (20 ng/ml) as well as with MTX (1.5 µM) and the glucocorticoids prednisolone (1 µM) and dexamethasone (1 µM). The interaction of both cell types under static conditions using a cell-to-cell-binding assay was analyzed. RASF adhesion to E-selectin was studied in a flow adhesion assay (flow rates: 18.4/30.5/60.5 ml/h) as flow conditions are required for selectins to be obtain their active conformation. The expression of selected adhesion molecules on RASF and EC after adipokine./MTX/glucocorticoid stimulation was analyzed by real-time PCR.
Prednisolone stimulation down-regulated mRNA expression of VCAM-1 (-3.3-fold) in RASF (n=3), which was also reduced after dexamethasone stimulation (‑8.3‑fold). TNF-α used as proinflammatory control increased ICAM-1 mRNA expression (46.5 fold), while P‑selectin mRNA expression (-7.7-fold) was decreased in EC (n=3).Under static conditions, the adipokines increased adhesion of RASF to EC (Ad: 37%, Vis: 23%, Res: 32%; n=6), while prednisolone 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 to E-selectin (-33%/-35%/-41%; n=3 for each flow rate).
Adipokines have an influence on the cellular expression of adhesion molecules on RASF and EC as well as their interaction. Adipokines increase adhesion of RASF to EC and therefore influence RASF migration. Therapeutics such as glucocorticoids and MTX antagonized these effects, which may represent a mechanism of the protective effects of these drugs observed in patients. Evaluation of the immunomodulatory role of adipokines and therapeutics in the pathogenesis and progression of RA may help to understand new metabolic-inflammatory pathways active in chronic inflammatory diseases such as RA.
To cite this abstract in AMA style:Hasseli R, Frommer KW, Umscheid T, Schönburg M, Rehart S, Müller-Ladner U, Neumann E. The Influence of Adipokines on the Interaction of Rheumatoid Arthritis Synovial Fibroblasts with Endothelial Cells [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/the-influence-of-adipokines-on-the-interaction-of-rheumatoid-arthritis-synovial-fibroblasts-with-endothelial-cells/. Accessed October 14, 2019.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-influence-of-adipokines-on-the-interaction-of-rheumatoid-arthritis-synovial-fibroblasts-with-endothelial-cells/