Adipokines and Inflammation Alter the Interaction Between Rheumatoid Arthritis Synovial Fibroblasts and Endothelial Cells
Objective: The long-distance migration of rheumatoid arthritis synovial fibroblasts (RASFs) in the severe combined immunodeficiency (SCID) mouse model of rheumatoid arthritis (RA) suggests that an interaction between RASFs and endothelial cells (EC) is critical in this process. Our objective was to...
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| Format: | Article |
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Frontiers Media S.A.
2020-06-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2020.00925/full |
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| author | Rebecca Hasseli Klaus W. Frommer Maria Schwarz Marie-Lisa Hülser Carina Schreiyäck Mona Arnold Magnus Diller Ingo H. Tarner Uwe Lange Joern Pons-Kühnemann Markus Schönburg Stefan Rehart Ulf Müller-Ladner Elena Neumann |
| author_facet | Rebecca Hasseli Klaus W. Frommer Maria Schwarz Marie-Lisa Hülser Carina Schreiyäck Mona Arnold Magnus Diller Ingo H. Tarner Uwe Lange Joern Pons-Kühnemann Markus Schönburg Stefan Rehart Ulf Müller-Ladner Elena Neumann |
| author_sort | Rebecca Hasseli |
| collection | DOAJ |
| description | Objective: The long-distance migration of rheumatoid arthritis synovial fibroblasts (RASFs) in the severe combined immunodeficiency (SCID) mouse model of rheumatoid arthritis (RA) suggests that an interaction between RASFs and endothelial cells (EC) is critical in this process. Our objective was to assess whether immunomodulatory factors such as adipokines and antirheumatic drugs affect the adhesion of RASFs to ECs or the expression of surface molecules.Methods: Primary ECs or human umbilical vein endothelial cell (HUVEC) and primary RASFs were stimulated with adiponectin (10 μg/mL), visfatin (100 ng/mL), and resistin (20 ng/mL) or treated with methotrexate (1.5 and 1,000 μM) and the glucocorticoids prednisolone (1 μM) and dexamethasone (1 μM), respectively. The expression of adhesion molecules was analyzed by real-time polymerase chain reaction. The interaction of both cell types was analyzed under static (cell-to-cell binding assay) and dynamic conditions (flow-adhesion assay).Results: Under static conditions, adipokines increased mostly binding of RASFs to EC (adiponectin: 40%, visfatin: 28%, tumor necrosis factor α: 49%). Under flow conditions, visfatin increased RASF adhesion to HUVEC (e.g., 0.5 dyn/cm2: 75.2%). Reduced adhesion of RASFs to E-selectin was observed after treatment with dexamethasone (e.g., 0.9 dyn/cm2: −40%). In ECs, tumor necrosis factor α (TNF-α) increased expression of intercellular adhesion molecule 1 (20-fold) and vascular cell adhesion molecule 1 (77-fold), whereas P-selectin was downregulated after stimulation with TNF-α (−6-fold).Conclusion: The adhesion of RASFs to EC was increased by visfatin under static and flow conditions, whereas glucocorticoids were able to decrease adhesion to E-selectin. The process of migration and adhesion of RASFs to ECs could be enhanced by adipokines via adhesion molecules and seems to be targeted by therapeutic intervention with glucocorticoids. |
| first_indexed | 2024-12-13T00:04:41Z |
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| id | doaj.art-cce0eb82468d4deb8c6544bb1f3e8fee |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-13T00:04:41Z |
| publishDate | 2020-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-cce0eb82468d4deb8c6544bb1f3e8fee2022-12-22T00:06:19ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-06-011110.3389/fimmu.2020.00925508598Adipokines and Inflammation Alter the Interaction Between Rheumatoid Arthritis Synovial Fibroblasts and Endothelial CellsRebecca Hasseli0Klaus W. Frommer1Maria Schwarz2Marie-Lisa Hülser3Carina Schreiyäck4Mona Arnold5Magnus Diller6Ingo H. Tarner7Uwe Lange8Joern Pons-Kühnemann9Markus Schönburg10Stefan Rehart11Ulf Müller-Ladner12Elena Neumann13Department of Internal Medicine and Rheumatology, Justus-Liebig-University Giessen, Kerckhoff, Bad Nauheim, GermanyDepartment of Internal Medicine and Rheumatology, Justus-Liebig-University Giessen, Kerckhoff, Bad Nauheim, GermanyDepartment of Internal Medicine and Rheumatology, Justus-Liebig-University Giessen, Kerckhoff, Bad Nauheim, GermanyDepartment of Internal Medicine and Rheumatology, Justus-Liebig-University Giessen, Kerckhoff, Bad Nauheim, GermanyDepartment of Internal Medicine and Rheumatology, Justus-Liebig-University Giessen, Kerckhoff, Bad Nauheim, GermanyDepartment of Internal Medicine and Rheumatology, Justus-Liebig-University Giessen, Kerckhoff, Bad Nauheim, GermanyDepartment of Internal Medicine and Rheumatology, Justus-Liebig-University Giessen, Kerckhoff, Bad Nauheim, GermanyDepartment of Internal Medicine and Rheumatology, Justus-Liebig-University Giessen, Kerckhoff, Bad Nauheim, GermanyDepartment of Internal Medicine and Rheumatology, Justus-Liebig-University Giessen, Kerckhoff, Bad Nauheim, GermanyMedical Statistics, Institute of Medical Informatics, Justus-Liebig University Giessen, Giessen, GermanyDepartment of Cardiac Surgery, Kerckhoff-Klinik, Bad Nauheim, GermanyDepartment of Orthopedics and Trauma Surgery, Agaplesion Markus Hospital, Frankfurt, GermanyDepartment of Internal Medicine and Rheumatology, Justus-Liebig-University Giessen, Kerckhoff, Bad Nauheim, GermanyDepartment of Internal Medicine and Rheumatology, Justus-Liebig-University Giessen, Kerckhoff, Bad Nauheim, GermanyObjective: The long-distance migration of rheumatoid arthritis synovial fibroblasts (RASFs) in the severe combined immunodeficiency (SCID) mouse model of rheumatoid arthritis (RA) suggests that an interaction between RASFs and endothelial cells (EC) is critical in this process. Our objective was to assess whether immunomodulatory factors such as adipokines and antirheumatic drugs affect the adhesion of RASFs to ECs or the expression of surface molecules.Methods: Primary ECs or human umbilical vein endothelial cell (HUVEC) and primary RASFs were stimulated with adiponectin (10 μg/mL), visfatin (100 ng/mL), and resistin (20 ng/mL) or treated with methotrexate (1.5 and 1,000 μM) and the glucocorticoids prednisolone (1 μM) and dexamethasone (1 μM), respectively. The expression of adhesion molecules was analyzed by real-time polymerase chain reaction. The interaction of both cell types was analyzed under static (cell-to-cell binding assay) and dynamic conditions (flow-adhesion assay).Results: Under static conditions, adipokines increased mostly binding of RASFs to EC (adiponectin: 40%, visfatin: 28%, tumor necrosis factor α: 49%). Under flow conditions, visfatin increased RASF adhesion to HUVEC (e.g., 0.5 dyn/cm2: 75.2%). Reduced adhesion of RASFs to E-selectin was observed after treatment with dexamethasone (e.g., 0.9 dyn/cm2: −40%). In ECs, tumor necrosis factor α (TNF-α) increased expression of intercellular adhesion molecule 1 (20-fold) and vascular cell adhesion molecule 1 (77-fold), whereas P-selectin was downregulated after stimulation with TNF-α (−6-fold).Conclusion: The adhesion of RASFs to EC was increased by visfatin under static and flow conditions, whereas glucocorticoids were able to decrease adhesion to E-selectin. The process of migration and adhesion of RASFs to ECs could be enhanced by adipokines via adhesion molecules and seems to be targeted by therapeutic intervention with glucocorticoids.https://www.frontiersin.org/article/10.3389/fimmu.2020.00925/fulladipokinesendocrinefibroblastrheumatoid arthritisinflammationendothelium |
| spellingShingle | Rebecca Hasseli Klaus W. Frommer Maria Schwarz Marie-Lisa Hülser Carina Schreiyäck Mona Arnold Magnus Diller Ingo H. Tarner Uwe Lange Joern Pons-Kühnemann Markus Schönburg Stefan Rehart Ulf Müller-Ladner Elena Neumann Adipokines and Inflammation Alter the Interaction Between Rheumatoid Arthritis Synovial Fibroblasts and Endothelial Cells Frontiers in Immunology adipokines endocrine fibroblast rheumatoid arthritis inflammation endothelium |
| title | Adipokines and Inflammation Alter the Interaction Between Rheumatoid Arthritis Synovial Fibroblasts and Endothelial Cells |
| title_full | Adipokines and Inflammation Alter the Interaction Between Rheumatoid Arthritis Synovial Fibroblasts and Endothelial Cells |
| title_fullStr | Adipokines and Inflammation Alter the Interaction Between Rheumatoid Arthritis Synovial Fibroblasts and Endothelial Cells |
| title_full_unstemmed | Adipokines and Inflammation Alter the Interaction Between Rheumatoid Arthritis Synovial Fibroblasts and Endothelial Cells |
| title_short | Adipokines and Inflammation Alter the Interaction Between Rheumatoid Arthritis Synovial Fibroblasts and Endothelial Cells |
| title_sort | adipokines and inflammation alter the interaction between rheumatoid arthritis synovial fibroblasts and endothelial cells |
| topic | adipokines endocrine fibroblast rheumatoid arthritis inflammation endothelium |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2020.00925/full |
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