TNF inhibits catecholamine production from induced sympathetic neuron-like cells in rheumatoid arthritis and osteoarthritis in vitro
- Synovial adipose stem cells (sASC) can be differentiated into catecholamine-expressing sympathetic neuron-like cells to treat experimental arthritis. However, the pro-inflammatory tumor necrosis factor (TNF) is known to be toxic to catecholaminergic cells (see Parkinson disease), and this may prevent anti-inflammatory effects in inflamed tissue. We hypothesized that TNF exhibits inhibitory effects on human differentiated sympathetic tyrosine hydroxylase-positive (TH+) neuron-like cells. For the first time, iTH+ neuron-like sympathetic cells were generated from sACSs of rheumatoid arthritis (RA) and osteoarthritis (OA) synovial tissue. Compared to untreated controls in both OA and RA, TNF-treated iTH+ cells demonstrated a weaker staining of catecholaminergic markers in cell cultures of RA/OA patients, and the amount of produced noradrenaline was markedly lower. These effects were reversed by etanercept. Exposure of iTH+ cells to synovial fluid of RA patients showed similar inhibitory effects. In mixed synovial cells, significant effects of TNF on catecholamine release were observed only in OA. This study shows that TNF inhibits iTH+ synovial cells leading to the decrease of secreted noradrenaline. This might be a reason why discovered newly appearing TH+ cells in the synovium are not able to develop their possible full anti-inflammatory role in arthritis.
Author: | Markus Herrmann, Sven Anders, Rainer H. StraubORCiDGND, Zsuzsa Jenei-LanzlORCiDGND |
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URN: | urn:nbn:de:hebis:30:3-571194 |
DOI: | https://doi.org/10.1038/s41598-018-27927-8 |
ISSN: | 2045-2322 |
Parent Title (German): | Scientific Reports |
Publisher: | Macmillan Publishers Limited, part of Springer Nature |
Place of publication: | London |
Document Type: | Article |
Language: | English |
Date of Publication (online): | 2018/06/25 |
Date of first Publication: | 2018/06/25 |
Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
Release Date: | 2021/09/22 |
Volume: | 8 |
Issue: | Article number 9645 |
Page Number: | 13 |
HeBIS-PPN: | 488959616 |
Institutes: | Medizin / Medizin |
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Sammlungen: | Universitätspublikationen |
Licence (German): | Creative Commons - Namensnennung 4.0 |