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15. Endogenously produced catecholamines improve the regulatory function of TLR9-activated B cells

Author

Honke, Nadine, Lowin, Torsten, Opgenoorth, Birgit, Shaabani, Namir, Lautwein, Alexander, Teijaro, John R., Schneider, Matthias, and Pongratz, Georg

Subjects
Male, rheumatoid arthritis, B Cells, Lymphocyte Activation, Biochemistry, Immune Receptors, B7-H1 Antigen, Arthritis, Rheumatoid, Mice, White Blood Cells, Catecholamines, Mathematical and Statistical Techniques, Spectrum Analysis Techniques, Animal Cells, tyrosine hydroxylase, Medicine and Health Sciences, Amines, Enzyme-Linked Immunoassays, Biology (General), Toll-like Receptors, Mice, Knockout, B-Lymphocytes, Regulatory, Immune System Proteins, Organic Compounds, T Cells, General Neuroscience, Statistics, Neurochemistry, Neurotransmitters, Flow Cytometry, Interleukin-10, Chemistry, Spectrophotometry, Physical Sciences, Collagen, Cytophotometry, Cellular Types, General Agricultural and Biological Sciences, Research Article, Signal Transduction, Biogenic Amines, Fas Ligand Protein, Tyrosine 3-Monooxygenase, QH301-705.5, Immune Cells, Immunology, autoimmune disease, Research and Analysis Methods, General Biochemistry, Genetics and Molecular Biology, Animals, Statistical Methods, Antibody-Producing Cells, Molecular Biology Techniques, Immunoassays, Molecular Biology, Analysis of Variance, Blood Cells, General Immunology and Microbiology, Organic Chemistry, Chemical Compounds, Biology and Life Sciences, Proteins, Cell Biology, regulatory B cells, Arthritis, Experimental, Hormones, Disease Models, Animal, Toll-Like Receptor 9, Immunologic Techniques, Mathematics, Neuroscience, Cloning
Abstract

The sympathetic nervous system (SNS) contributes to immune balance by promoting anti-inflammatory B cells. However, whether B cells possess a self-regulating mechanism by which they modulate regulatory B cell (Breg) function is not well understood. In this study, we investigated the ability of B cells to synthesize their own catecholamines upon stimulation with different B cell activators and found that expression of the enzyme tyrosine hydroxylase (TH), required to generate catecholamines, is up-regulated by Toll-like receptor (TLR)9. This TLR9-dependent expression of TH correlated with up-regulation of adrenergic receptors (ADRs), enhanced interleukin (IL)-10 production, and overexpression of the co-inhibitory ligands programmed death ligand 1 (PD-L1) and Fas ligand (FasL). Moreover, concomitant stimulation of ß1-3-ADRs together with a B cell receptor (BCR)/TLR9 stimulus clearly enhances the anti-inflammatory potential of Bregs to suppress CD4 T cells, a crucial population in the pathogenesis of autoimmune diseases, like rheumatoid arthritis (RA). Furthermore, TH up-regulation was also demonstrated in B cells during the course of collagen-induced arthritis (CIA), a mouse model for the investigation of RA. In conclusion, our data show that B cells possess an autonomous mechanism to modulate their regulatory function in an autocrine and/or paracrine manner. These findings help to better understand the function of B cells in the regulation of autoimmune diseases and the interplay of SNS., The sympathetic nervous system produces neurotransmitters such as catecholamines which contribute to immune balance by promoting anti-inflammatory B cells. This study shows that mouse B cells can themselves synthesize, sense, and transport catecholamines, which in turn modulate regulatory B cell function in an autocrine and/or paracrine manner to suppress T cell proliferation. more...

Published
2022

19. Vascular smooth muscle cells of human aorta express CXCL17 - a possible mechanism for cell recruitment in GCA

Author

Kernder, Anna Luise, Mucke, Johanna, Tang-Chieu, Long, Bleck, Dennis, Lowin, Torsten, Akhyari, Payam, Bleck, Ellen, Heier, Claudia, Pongratz, Georg, Schneider, Matthias, and Vordenbäumen, Stefan

Subjects
ddc: 610, immune system diseases, cardiovascular system, cardiovascular diseases, 610 Medical sciences, Medicine, skin and connective tissue diseases
Abstract

Introduction: Giant cell arteritis (GCA) is characterized by an increased release of IFN-γ by Th1 cells and dendritic cells accompanied by an invasion of lymphocytes, dendritic cells and monocytes. The mechanisms contributing to cellular trafficking in GCA are incompletely understood. The most[for full text, please go to the a.m. URL], Deutscher Rheumatologiekongress 2020, 48. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh), 34. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh) more...

Published
2020

20. Characterization of B- and T-Cell Compartment and B-Cell Related Factors Belonging to the TNF/TNFR Superfamily in Patients With Clinically Active Systemic Lupus Erythematosus: Baseline BAFF Serum Levels Are the Strongest Predictor of Response to Belimumab after Twelve Months of Therapy

Author

Piantoni, Silvia, primary, Regola, Francesca, additional, Masneri, Stefania, additional, Merletti, Michele, additional, Lowin, Torsten, additional, Airò, Paolo, additional, Tincani, Angela, additional, Franceschini, Franco, additional, Andreoli, Laura, additional, and Pongratz, Georg, additional more...

Published
2021
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26. Contributors

Author

Abate, C., Adeghate, Ernest, Afroze, Chowdhury Alfi, Ahmed, Md Nasir, Ahmed, Mohammed M., Anand, Rajsavi Singh, Armour, Mike, Askari, Vahid Reza, Azam, Md Nur Kabidul, Bahnson, Edward Moreira, Baradaran Rahimi, Vafa, Barr, Alasdair M., Boivin, Michael, Brown, Joshua, Budde, Henning, Camacho-Rivera, Marlene, Chen, Ye, Chesworth, Rose, Cheung, Chi Wai, Chmura, Stacey E., Christiansen, April L., Clark, Thomas M., Colabufo, N.A., Contino, M., Costi, Roberta, Crescioli, Giada, da Silva-Júnior, Rui Milton Patrício, del Río, Carmen, Di Santo, Roberto, Duffy, Bryan C., Dyck, Jason R.B., Echeverry, Carolina, Eurich, Dean T., Fagetti, Jimena, Feingold, Daniel, Feng, Hui, Fernández-Carballido, Ana, Feuerstein, Joseph D., Filho, Alberto Souza Sá, Firenzuoli, Fabio, Fraguas-Sánchez, Ana Isabel, Garcia-Cairasco, Norberto, García-Fuster, M. Julia, García-García, Fabio, Garg, Ayushi, Gengo, Fran M., Gliksberg, Or, Gómez-Nieto, Ricardo, González-Mariscal, Isabel, Götz, Marcus R, Gyamfi, Daniel, Hagerman, Randi, Hashiesh, Hebaallah Mamdouh, Hernandez-Ortega, Nicolas, Hesami, Mohsen, Imperatori, Claudio, Islam, Jessica Y., Jahan, Rownak, Jha, Niraj Kumar, Jiang, Jessica XR, Johnson, Devon, Jones, Andrew Maxwell Phineas, Judd, Christopher D., Karl, Tim, Kaur, Ramanpreet, Kaushal, Naveen, Khan, Maria, Kumar, Sanjay, Kumar, Ujendra, Laws, III, John Staton, Lazarini-Lopes, Willian, Lee, Cerina, Leonetti, F., Leszko, Magdalena, Li, Lingyun, Linher-Melville, Katja, Lo, Lindsay A., Lombardi, Niccolò, López, Dolores E., Lowin, Torsten, Lyzwinski, Lynnette Nathalie, MacCallum, Caroline A., Machado, Sergio, Madia, Valentina Noemi, Maggini, Valentina, Mattle, Anna G., McLemon, Erin, Mechoulam, Raphael, Mehmood, Ishrat, Memarzia, Arghavan, Müller-Vahl, Kirsten R., Muñoz, Eduardo, Murillo-Rodríguez, Eric, Muschett, Matthew, Musetti, Bruno, Ojha, Shreesh, Patel, Vinood B., Paul, Tridib K., Piasek, Adrianna Maria, Pistawka, Carly A., Preedy, Victor R., Purcell, Chad, Rahmatullah, Mohammed, Rajendram, Rajkumar, Ralyea, Jr., Christopher C., Raup-Konsavage, Wesley M., Reyes-Parada, Miguel, Rodriguez, Diane L., Rosenthal, Martha S., Sadek, Bassem, Saleh, Ruba A., Scorza, Cecilia, Sera, Leah, Servilha-Menezes, Gabriel, Sharma, Tanvi, Shirah, Bader H., Shrestha, Srijan, Sinclair, Justin, Singh, Gurmit, Singh, Sneha, Smid, Scott D., Snider-Adler, Melissa, Sobiepanek, Anna, Somvanshi, Rishi K., Stefanachi, A., Stevenson, Maximillian H., Szejko, Natalia, Tanco, Kimberson, Thomas, Shilu Deepa, Thomson, Leonor, Torres-Suárez, Ana Isabel, Torterolo, Pablo, Valverde, Olga, Vannacci, Alfredo, Viana-Torre, Gerardo, Vidot, Denise C., Vrana, Kent E., Winkler, Matthias, Wong, Stanley Sau-Ching, Yadollahpour, Ali, and Yamamoto, Tetsuya more...

Published
2023
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28. Impact of Δ 9 -Tetrahydrocannabinol on Rheumatoid Arthritis Synovial Fibroblasts Alone and in Co-Culture with Peripheral Blood Mononuclear Cells.

Author

Lowin, Torsten, Kok, Christina, Smutny, Sophie, and Pongratz, Georg

Subjects
MONONUCLEAR leukocytes, RHEUMATOID arthritis, FIBROBLASTS, TUMOR necrosis factors, EXPERIMENTAL arthritis
Abstract

δ9-Tetrahydrocannabinol (THC) has demonstrated anti-inflammatory effects in animal models of arthritis, but its mechanism of action and cellular targets are still unclear. The purpose of this study is to elucidate the effects of THC (0.1–25 µM) on synovial fibroblasts from patients with rheumatoid arthritis (RASF) and peripheral blood mononuclear cells (PBMC) from healthy donors in respect to proliferation, calcium mobilization, drug uptake, cytokine and immunoglobulin production. Intracellular calcium and drug uptake were determined by fluorescent dyes Cal-520 and PoPo3, respectively. Cytokine and immunoglobulin production were evaluated by ELISA. Cannabinoid receptors 1 and 2 (CB1 and CB2) were detected by flow cytometry. RASF express CB1 and CB2 and the latter was increased by tumor necrosis factor (TNF). In RASF, THC (≥5 µM) increased intracellular calcium levels/PoPo3 uptake in a TRPA1-dependent manner and reduced interleukin-8 (IL-8) and matrix metalloprotease 3 (MMP-3) production at high concentrations (25 µM). Proliferation was slightly enhanced at intermediate THC concentrations (1–10 µM) but was completely abrogated at 25 µM. In PBMC alone, THC decreased interleukin-10 (IL-10) production and increased immunoglobulin G (IgG). In PBMC/RASF co-culture, THC decreased TNF production when cells were stimulated with interferon-γ (IFN-γ) or CpG. THC provides pro- and anti-inflammatory effects in RASF and PBMC. This is dependent on the activating stimulus and concentration of THC. Therefore, THC might be used to treat inflammation in RA but it might need titrating to determine the effective concentration. [ABSTRACT FROM AUTHOR] more...

Published
2022
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30. The ghrelin system is regulated by nutrient availability and pro-inflammatory cytokines in rheumatoid arthritis synovial fibroblasts

Author

Lowin, Torsten, Lesmann, Hellen, Oebels, Benjamin, Schneider, Matthias, and Pongratz, Georg

Subjects
ddc: 610, digestive, oral, and skin physiology, 610 Medical sciences, Medicine, hormones, hormone substitutes, and hormone antagonists
Abstract

Background: Ghrelin is an orexigenic neuropeptide and its levels are decreased in patients with rheumatoid arthritis. Ghrelin downregulates pro-inflammatory cytokine production in T cells and monocytes and could therefore be beneficial to treat chronic inflammatory diseases. Synovial fibroblasts are[for full text, please go to the a.m. URL], 47. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh), 33. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh), 29. Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR) more...

Published
2019

31. Fibroblast like synoviocytes (FLS) are capable of inducing class switch recombination (CSR) in naive B cells from healthy donors; the process appears to be IL-6 and CD40L dependent

Author

Bleck, Dennis, Pongratz, Georg, Schneider, Matthias, and Lowin, Torsten

Subjects
musculoskeletal diseases, ddc: 610, 610 Medical sciences, Medicine
Abstract

Background: Rheumatoid Arthritis (RA) is a disease characterized by chronic inflammation of the synovial tissue in joints. It is driven by highly activated B cells. Synovial cells, primarily Fibroblast like synoviocytes (FLS) play an important role in activating these B cells. It was previously shown,[for full text, please go to the a.m. URL], 47. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh), 33. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh), 29. Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR) more...

Published
2019

32. Regulation and function of TNF family member receptors and ligands in rheumatoid arthritis synovial fibroblasts

Author

Lowin, Torsten, Schneider, Matthias, and Pongratz, Georg

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

Background: Rheumatoid arthritis (RA) synovial fibroblasts (SF) show an activated, invasive phenotype which is accompanied by copious production of pro-inflammatory cytokines. In addition, RASF have been shown to stimulate B cell survival by the production of BAFF (CD257). While the role for TNF family[for full text, please go to the a.m. URL], 46. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh), 32. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh), Wissenschaftliche Herbsttagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR) more...

Published
2019

38. Association Between Changes in BLyS Levels and the Composition of B and T Cell Compartments in Patients With Refractory Systemic Lupus Erythematosus Treated With Belimumab

Author

Regola, Francesca, primary, Piantoni, Silvia, additional, Lowin, Torsten, additional, Archetti, Silvia, additional, Reggia, Rossella, additional, Kumar, Rajesh, additional, Franceschini, Franco, additional, Airò, Paolo, additional, Tincani, Angela, additional, Andreoli, Laura, additional, and Pongratz, Georg, additional more...

Published
2019
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40. Expression von CXCL17 und Actin in der Media synovialer Gefäße: Anwendungsbeispiel einer molekularen Lokalisationsdiagnostik an kryokonservierter Synovialis mittels in situ Hybridisation/Immunfluoreszenz-Doppelfärbung

Author

Tang-Chieu, Long, Bleck, Ellen, Pauly, Thomas, Mucke, Johanna, Lowin, Torsten, Pongratz, Georg, Schneider, Matthias, and Vordenbäumen, Stefan

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

Einleitung: CXCL17 ist das zuletzt identifizierte und am wenigsten erforschte Chemokin. Bekannt sind chemotaktische Eigenschaften auf Neutrophile, Monozyten und eine Induktion der Angiogenese. Vielen Chemokinen wird eine Bedeutung in der Pathogenese der rheumatoiden Arthritis (RA) beigemessen (z.B. [zum vollständigen Text gelangen Sie über die oben angegebene URL], 45. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh), 31. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh), 27. Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR) more...

Published
2017

41. Differential influence of synovial fibroblasts from osteoarthritis vs. rheumatoid arthritis patients on B cell survival and immunoglobulin production

Author

Bleck, Dennis, Lowin, Torsten, Schneider, Matthias, and Pongratz, Georg

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

Background: Rheumatoid Arthritis (RA) is a disease characterized by chronic inflammation of the synovial tissue in joints. It is driven by highly activated B cells. Synovial cells, primarily synovial Fibroblasts (SF) play an important role in activating these B cells. In order to investigate the interactions[for full text, please go to the a.m. URL], 45. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh), 31. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh), 27. Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR) more...

Published
2017
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42. Activation in vivo and in vitro increases responsiveness to catecholamines and regulatory potential of B cells by increasing IL-10 in a p38- and Gi-dependent manner

Author

Pongratz, Georg, Krebber, Katharina, Straub, Rainer H., Schneider, Matthias, and Lowin, Torsten

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

Background: Splenic B cells from collagen-induced arthritis (CIA) mice react to a beta2-adrenoceptor (AR) stimulus with increased IL-10 production and adoptive transfer of these cells decreases disease activity. However, B cells from unimmunized mice do not adequately increase IL-10. Therefore, we test[for full text, please go to the a.m. URL], 45. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh), 31. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh), 27. Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR) more...

Published
2017
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43. Comprehensive Longitudinal Surveillance of the IgG Autoantibody Repertoire in Established Systemic Lupus Erythematosus

Author

Vordenbäumen, Stefan, primary, Brinks, Ralph, additional, Hoyer, Annika, additional, Fischer‐Betz, Rebecca, additional, Pongratz, Georg, additional, Lowin, Torsten, additional, Zucht, Hans‐Dieter, additional, Budde, Petra, additional, Bleck, Ellen, additional, Schulz‐Knappe, Peter, additional, and Schneider, Matthias, additional more...

Published
2019
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44. Anti-inflammatory effects of N-acylethanolamines in rheumatoid arthritis synovial cells are mediated by TRPV1 and TRPA1 in a COX-2 dependent manner

Author

Lowin, Torsten, Apitz, Martin, Anders, Sven, and Straub, Rainer H.

Subjects
Male, Tumor necrosis factor, Immunology, Anti-Inflammatory Agents, 610 Medizin, TRPV Cation Channels, Interleukin 6, Nerve Tissue Proteins, Interleukin 8, TRPA1, Matrix metalloproteinase 3, Arthritis, Rheumatoid, Mice, Transient Receptor Potential Channels, Rheumatology, Immunology and Allergy, Animals, Humans, Synovial fibroblasts, TRPA1 Cation Channel, Cells, Cultured, Synoviocytes, TRPV1, Cannabinoids, Anandamide, Collagen-induced arthritis, Aged, ddc:610, Cyclooxygenase 2 Inhibitors, Dose-Response Relationship, Drug, Synovial Membrane, Middle Aged, Cyclooxygenase 2, Ethanolamines, Mice, Inbred DBA, Female, lipids (amino acids, peptides, and proteins), Calcium Channels, Inflammation Mediators, Research Article
Abstract

Introduction The endocannabinoid system modulates function of immune cells and mesenchymal cells such as fibroblasts, which contribute to cartilage destruction in rheumatoid arthritis (RA). The aim of the study was to determine the influence of N-acylethanolamines anandamide (AEA), palmitoylethanolamine (PEA) and oleylethanolamine (OEA) on several features of arthritic inflammation in vitro (human material) and in vivo (a mouse model). Methods Immunofluorescence and western blotting were used to detect cannabinoid receptors and related enzymes. Cytokines and MMP-3 were measured by ELISA. Intracellular signaling proteins were detected by proteome profiling. Proliferation was quantified by CTB reagent. Adhesion was assessed by the xCELLigence system. After onset of collagen type II arthritis, mice were treated daily with the FAAH inhibitor JNJ1661010 (20 mg/kg) or vehicle. Results IL-6, IL-8 and MMP-3 (determined only in synovial fibroblasts (SFs)) were downregulated in primary synoviocytes and SFs of RA and OA after AEA, PEA and OEA treatment. In SFs, this was due to activation of TRPV1 and TRPA1 in a COX-2-dependent fashion. FAAH inhibition increased the efficacy of AEA in primary synoviocytes but not in SFs. The effects of OEA and PEA on SFs were diminished by FAAH inhibition. Adhesion to fibronectin was increased in a CB1-dependent manner by AEA in OASFs. Furthermore, elevation of endocannabinoids ameliorated collagen-induced arthritis in mice. Conclusions N-acylethanolamines exert anti-inflammatory effects in SFs. A dual FAAH/COX-2 inhibitor, increasing N-acylethanolamine levels with concomitant TRP channel desensitization, might be a good candidate to inhibit the production of proinflammatory mediators of synovial cells and to reduce erosions. Electronic supplementary material The online version of this article (doi:10.1186/s13075-015-0845-5) contains supplementary material, which is available to authorized users. more...

Published
2015

45. Cannabinoid-based drugs targeting CB 1 and TRPV1, the sympathetic nervous system, and arthritis

Author

Lowin, Torsten and Straub, Rainer H.

Subjects
ddc:610, 610 Medizin
Abstract

Chronic inflammation in rheumatoid arthritis (RA) is accompanied by activation of the sympathetic nervous system, which can support the immune system to perpetuate inflammation. Several animal models of arthritis already demonstrated a profound influence of adrenergic signaling on the course of RA. Peripheral norepinephrine release from sympathetic terminals is controlled by cannabinoid receptor type 1 (CB 1 ), which is activated by two major endocannabinoids (ECs), arachidonylethanolamine (anandamide) and 2-arachidonylglycerol. These ECs also modulate function of transient receptor potential channels (TRPs) located on sensory nerve fibers, which are abundant in arthritic synovial tissue. TRPs not only induce the sensation of pain but also support inflammation via secretion of pro-inflammatory neuropeptides. In addition, many cell types in synovial tissue express CB 1 and TRPs. In this review, we focus on CB 1 and transient receptor potential vanilloid 1 (TRPV1)-mediated effects on RA since most anti-inflammatory mechanisms induced by cannabinoids are attributed to cannabinoid receptor type 2 (CB 2 ) activation. We demonstrate how CB 1 agonism or antagonism can modulate arthritic disease. The concept of functional antagonism with continuous CB 1 activation is discussed. Since fatty acid amide hydrolase (FAAH) is a major EC-degrading enzyme, the therapeutic possibility of FAAH inhibition is studied. Finally, the therapeutic potential of ECs is examined since they interact with cannabinoid receptors and TRPs but do not produce central side effects. more...

Published
2015

46. Sex steroids and interleukin-1 inhibit interferon-gamma induced B cell activating factor of the tumor necrosis factor family (BAFF) in human synovial fibroblasts

Author

Pongratz, Georg, Bäuml, Marina, Straub, Rainer H., and Lowin, Torsten

Subjects
stomatognathic diseases, stomatognathic system, ddc: 610, immune system diseases, hemic and lymphatic diseases, 610 Medical sciences, Medicine, skin and connective tissue diseases
Abstract

Introduction: BAFF, a cytokine important for B cell survival, plays a role in several autoimmune diseases. In psoriasis arthritis, BAFF correlates with disease activity and inversely with testosterone, suggesting a role for sex hormones in BAFF regulation. Synovial fibroblasts (SFs) produce BAFF upon[for full text, please go to the a.m. URL], 43. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh); 29. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh); 25. wissenschaftliche Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR) more...

Published
2015

47. Proinflammatory receptor switch from Galphas to Galphai signaling in mixed RA synovial cells caused by the interaction of PDE4 and beta-arrestin

Author

Jenei-Lanzl, Zsuzsa, Zwingenberg, Janika, Lowin, Torsten, Anders, Sven, and Straub, Rainer H.

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

Introduction: In chronic inflammation, prevention of cAMP degradation by phosphodiesterase-4 (PDE4) inhibition can be anti-inflammatory therapy. However, PDE4 inhibition was not effective in rheumatoid arthritis (RA). Recent studies demonstrated that PDE4/β-arrestin interaction at β-adrenoceptors[for full text, please go to the a.m. URL], 43. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh); 29. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh); 25. wissenschaftliche Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR) more...

Published
2015

48. Characterization of the Thyroid Hormone System in Rheumatoid Arthritis

Author

Pörings, Anna-Sophia, Lowin, Torsten, Rauch, Luise, Späth, Tanja, Gräber, Angelika, and Straub, Rainer H.

Subjects
rheumatoid arthritis, thyroxin, ddc: 610, Thyroid hormones, TSH, 610 Medical sciences, Medicine, rT3, T3
Abstract

Background: Chronic inflammation is characterized by an energy appeal reaction supporting high energy demand of the activated immune system. Thyroid hormones are strongly associated with catabolic effects and are therefore important mediators of energy allocation. Until now, the role of thyroid hormones[for full text, please go to the a.m. URL], 42. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh); 28. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh); 24. wissenschaftliche Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR) more...

Published
2014
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50. Increased expression of dopamine receptors in synovial fibroblasts from patients with rheumatoid arthritis: inhibitory effects of dopamine on interleukin-8 and interleukin-6

Author

Capellino, Silvia, Cosentino, Marco, Luini, Alessandra, Bombelli, Raffaella, Lowin, Torsten, Cutolo, Maurizio, Marino, Franca, and Straub, Rainer H.

Subjects
Dopamine Plasma Membrane Transport Proteins, Tissue Inhibitor of Metalloproteinase-2, Cultured, Tissue Inhibitor of Metalloproteinase-1, Interleukin-6, Arthritis, Cells, Dopamine, Interleukin-8, Synovial Membrane, Fibroblasts, Receptors, Dopamine, Arthritis, Rheumatoid, Rheumatoid, Receptors, Osteoarthritis, Humans, Matrix Metalloproteinase 3, Cells, Cultured
Abstract

Observations in both animal models of arthritis and patients with rheumatoid arthritis (RA) suggest a role for dopamine and its receptors in RA. Because synovial fibroblasts (SFs) contribute to inflammation and joint destruction in RA, the aim of this study was to investigate dopaminergic pathways in SFs obtained from patients with RA and, for comparison, in SFs from patients with osteoarthritis (OA) undergoing knee joint replacement surgery.The expression of all dopamine receptors (D1 -D5 ) and dopamine transporter was assessed by immunofluorescence and immunohistochemical staining. The levels of dopamine receptor and tyrosine hydroxylase messenger RNA were measured by real-time polymerase chain reaction. The intracellular content of dopamine, its precursor, and its main metabolites was assayed by high-performance liquid chromatography. The influence of dopamine on proinflammatory interleukin-6 (IL-6) and IL-8, matrix metalloproteinase 3, and tissue inhibitor of metalloproteinases 1 (TIMP-1) and TIMP-2 was studied in SFs.SFs possess an intrinsic dopaminergic system, including dopamine receptors, dopamine transporter, and tyrosine hydroxylase, and contain dopamine, its precursor, and its main metabolites. SFs from patients with RA, in comparison with those from patients with OA, showed increased expression of dopamine receptors D1 and D5 , and exogenous dopamine strongly inhibited the production of IL-8 in patients with RA.SFs from patients with RA and patients with OA show a dopaminergic phenotype. The expression of D1-like dopamine receptors was higher in RASFs, and this increased expression may lead to antiinflammatory effects, as demonstrated by the expression of IL-8. Studies in animal models and patients with RA are needed to assess the therapeutic potential of endogenous, local production of dopamine in synoviocytes. more...

Published
2013