Jenei-Lanzl, Zsuzsa and Capellino, Silvia and Kees, Frieder and Fleck, Martin and Lowin, Torsten and Straub, Rainer H. (2015) Anti-inflammatory effects of cell-based therapy with tyrosine hydroxylase-positive catecholaminergic cells in experimental arthritis. ANNALS OF THE RHEUMATIC DISEASES, 74 (2). pp. 444-451. ISSN 0003-4967, 1468-2060
Full text not available from this repository. (Request a copy)Abstract
Objectives Studies in rheumatoid arthritis (RA), osteoarthritis (OA) and mice with arthritis demonstrated tyrosine hydroxylase-positive (TH+) cells in arthritic synovium and parallel loss of sympathetic nerve fibres. The exact function of TH+ cells and mode of TH induction are not known. Methods Synovial cells of RA/OA were isolated and cultured under normoxic/hypoxic conditions with/without stimulating enzyme cofactors of TH and inhibitors of TH. We studied TH expression and release of cytokines/catecholamines. In vivo function was tested by cell therapy with TH+ neuronal precursor cells (TH+ neuronal cells) in DBA/1 mice with collagen type II-induced arthritis (CIA). Results Compared with normoxic conditions, hypoxia increased TH protein expression and catecholamine synthesis and decreased release of tumour necrosis factor (TNF) in OA/RA synovial cells. This inhibitory effect on TNF was reversed by TH inhibition with alpha-methylpara-tyrosine (alpha MPT), which was particularly evident under hypoxic conditions. Incubation with specific TH cofactors (tetrahydrobiopterin and Fe2+) increased hypoxia-induced inhibition of TNF, which was also reversed by aMPT. To address a possible clinical role of TH+ cells, murine TH+ neuronal cells were generated from mesenchymal stem cells. TH+ neuronal cells exhibited a typical catecholaminergic phenotype. Adoptive transfer of TH+ neuronal cells markedly reduced CIA in mice, and 6-hydroxydopamine, which depletes TH+ cells, reversed this effect. Conclusions The anti-inflammatory effect of TH+ neuronal cells on experimental arthritis has been presented for the first time. In RA/OA, TH+ synovial cells have TH-dependent anti-inflammatory capacities, which are augmented under hypoxia. Using generated TH+ neuronal cells might open new avenues for cell-based therapy.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | MESENCHYMAL STEM-CELLS; COLLAGEN-INDUCED ARTHRITIS; TUMOR-NECROSIS-FACTOR; RHEUMATOID-ARTHRITIS; SYNOVIAL TISSUE; HYPOXIA; PHOSPHORYLATION; INFLAMMATION; DIFFERENTIATION; NOREPINEPHRINE; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I Chemistry and Pharmacy > Institute of Pharmacy |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 25 Jul 2019 08:47 |
| Last Modified: | 25 Jul 2019 08:47 |
| URI: | https://pred.uni-regensburg.de/id/eprint/6060 |
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