Document Detail

Catecholamine-producing cells in the synovial tissue during arthritis: modulation of sympathetic neurotransmitters as new therapeutic target.
MedLine Citation:
PMID:  20498218     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: The proinflammatory and anti-inflammatory role of the sympathetic nervous system in early and late inflammation is an unresolved paradox. A drastic loss of sympathetic nerve fibres in the synovial tissue of patients with rheumatoid arthritis (RA) has previously been demonstrated. The presence of tyrosine hydroxylase (TH)-positive cells in RA and osteoarthritis (OA) has been determined, but the role of these cells in inflammation is still unclear. OBJECTIVE: To characterise TH-positive cells in inflamed RA and OA synovial tissue and to study their role in inflammation. METHODS: Synovial samples were obtained from 32 patients with OA and 19 patients with RA and from 10 control patients. Synovial tissue samples were used for immunofluorescence staining. Synovial cells were isolated by tissue digestion and immediately used for cell culture. For in vivo experiments, collagen type-II arthritis in DBA/1J mice was induced. RESULTS: TH+ cells were present only in inflamed tissue and not in controls. Catecholamine-storing vesicles and vesicular monoamine transporter 2 (VMAT2) were identified in the synovial tissue. Experimental increase of cytoplasmic catecholamines by VMAT2 blockade strongly reduced tumour necrosis factor (TNF) independently of canonical extracellular β-adrenergic signalling. In addition, VMAT2 blockade increased cyclic AMP (cAMP) and cAMP responsive element binding protein, responsible for TNF inhibition. In vivo, appearance of VMAT2 positive cells was confirmed. VMAT2 blockade ameliorated inflammation also in vivo. CONCLUSIONS: This study demonstrates that local catecholamine-producing cells start to replace sympathetic nerve fibres around the onset of disease, and modulation of locally produced catecholamines has strong anti-inflammatory effects in vivo and in vitro.
Silvia Capellino; Marco Cosentino; Christine Wolff; Martin Schmidt; Joachim Grifka; Rainer H Straub
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-05-24
Journal Detail:
Title:  Annals of the rheumatic diseases     Volume:  69     ISSN:  1468-2060     ISO Abbreviation:  Ann. Rheum. Dis.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-09-22     Completed Date:  2010-10-15     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372355     Medline TA:  Ann Rheum Dis     Country:  England    
Other Details:
Languages:  eng     Pagination:  1853-60     Citation Subset:  IM    
Department of Internal Medicine I, Laboratory of Experimental Rheumatology and Neuroendocrino-Immunology, University Hospital, 93042 Regensburg, Germany.
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MeSH Terms
Adrenergic Fibers / metabolism,  pathology
Anti-Inflammatory Agents, Non-Steroidal / pharmacology,  therapeutic use
Arthritis, Experimental / drug therapy,  metabolism,  pathology
Arthritis, Rheumatoid / metabolism*,  pathology
Catecholamines / biosynthesis*
Cells, Cultured
Cytoplasm / metabolism
Drug Evaluation, Preclinical / methods
Mice, Inbred DBA
Middle Aged
Neurotransmitter Agents / metabolism*
Osteoarthritis, Knee / metabolism*,  pathology
Reserpine / pharmacology,  therapeutic use
Synovial Membrane / innervation,  metabolism*,  pathology
Tumor Necrosis Factor-alpha / antagonists & inhibitors,  metabolism
Tyrosine 3-Monooxygenase / metabolism
U937 Cells
Reg. No./Substance:
0/Anti-Inflammatory Agents, Non-Steroidal; 0/Catecholamines; 0/Neurotransmitter Agents; 0/Tumor Necrosis Factor-alpha; 50-55-5/Reserpine; EC 3-Monooxygenase

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