Anti-inflammatory effects of endogenously released adenosine in synovial cells of osteoarthritis and rheumatoid arthritis patients

  • Exogenous adenosine and its metabolite inosine exert anti-inflammatory effects in synoviocytes of osteoarthritis (OA) and rheumatoid arthritis (RA) patients. We analyzed whether these cells are able to synthesize adenosine/inosine and which adenosine receptors (ARs) contribute to anti-inflammatory effects. The functionality of synthesizing enzymes and ARs was tested using agonists/antagonists. Both OA and RA cells expressed CD39 (converts ATP to AMP), CD73 (converts AMP to adenosine), ADA (converts adenosine to inosine), ENT1/2 (adenosine transporters), all AR subtypes (A1, A2A, A2B and A3) and synthesized predominantly adenosine. The CD73 inhibitor AMPCP significantly increased IL-6 and decreased IL-10 in both cell types, while TNF only increased in RA cells. The ADA inhibitor DAA significantly reduced IL-6 and induced IL-10 in both OA and RA cells. The A2AAR agonist CGS 21680 significantly inhibited IL-6 and induced TNF and IL-10 only in RA, while the A2BAR agonist BAY 60-6583 had the same effect in both OA and RA. Taken together, OA and RA synoviocytes express the complete enzymatic machinery to synthesize adenosine/inosine; however, mainly adenosine is responsible for the anti- (IL-6 and IL-10) or pro-inflammatory (TNF) effects mediated by A2A- and A2BAR. Stimulating CD39/CD73 with simultaneous ADA blockage in addition to TNF inhibition might represent a promising therapeutic strategy.

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Author:Rebecca Sohn, Marius Junker, Andrea MeurerORCiD, Frank Zaucke, Rainer H. Straub, Zsuzsa Jenei-Lanzl
Parent Title (English):International journal of molecular sciences
Publisher:Molecular Diversity Preservation International
Place of publication:Basel
Document Type:Article
Date of Publication (online):2021/08/19
Date of first Publication:2021/08/19
Publishing Institution:Universit├Ątsbibliothek Johann Christian Senckenberg
Release Date:2021/09/22
Tag:adenosine; inflammation; inosine; osteoarthritis; rheumatoid arthritis; synoviocytes
Issue:16, art. 8956
Page Number:18
First Page:1
Last Page:18
This research was funded by the Deutsche Forschungsgemeinschaft FOR2407 (JE 642/4-2 to Z.J.-L. (project number 277277765)), STR 511/32-1 to R.H.S. (project number 243785207), and FOR2722 (FZ 561/3-1 to F.Z. (project number 407168728).
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0