Background/Purpose:

In recent studies we demonstrated that catecholamines produced by tyrosine-hydroxylase-positive (TH+) synovial cells are able to mediate anti-inflammatory effects in rheumatoid arthritis (RA).^a TNF has been shown to be toxic to catecholaminergic neurons in Parkinson´s disease (PD).^b Therefore, the aim of this study was to analyze whether TNF exhibits also inhibitory effects on TH in the chronic inflamed synovium.

Methods:

Human mixed synovial cells were isolated from RA and osteoarthritis (OA) patients and “induced TH+ cells” (iTH+) were generated from human mesenchymal stem cells (MSC) as described previously.^a Cells were cultivated under hypoxia (1% O₂), because the microenvironment of inflamed joints is hypoxic. TNF and the anti-TNF etanercept were administered in different concentrations and combinations. Expression and activity of TH was analyzed by immunofluorescence and TH activity assay. In addition, catecholamines were quantified via HPLC and the quality of catecholaminergic differentiation was investigated staining VMAT2, Nurr1, and βIII tubulin as markers.

Results:

In mixed synovial cell culture, TNF inhibited TH activity and catecholamine synthesis compared to untreated control in both OA and RA. In general, TNF did not disturb catecholaminergic differentiation of MSCs to iTH+ cells. However, TH staining of TNF-treated iTH+ cells was weaker, the TH activity and the amount of produced catecholamines lower. Similarly, expression of VMAT2, Nurr1, and βIII tubulin decreased after TNF-treatment in iTH+ cells. The effects of TNF were reversed by etanercept in both synovial cell and iTH+ cell cultures.

Conclusion:

This study shows TNF inhibition of TH expression and activity in TH+ synovial cells and differentiating iTH+ cells leading to the decrease of anti-inflammatory acting catecholamines. This might be a reason why resident synovial TH+ cells are not able to unfold their anti-inflammatory effects in RA.

« Back to 2015 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/influence-of-tnf-on-anti-inflammatory-tyrosine-hydroxylase-positive-synovial-cells-in-rheumatoid-arthritis-and-osteoarthritis/