TY  - JOUR
A1  - Sohn, Rebecca
A1  - Junker, Marius
A1  - Meurer, Andrea
A1  - Zaucke, Frank
A1  - Straub, Rainer H.
A1  - Jenei-Lanzl, Zsuzsa
T1  - Anti-inflammatory effects of endogenously released adenosine in synovial cells of osteoarthritis and rheumatoid arthritis patients
T2  - International journal of molecular sciences
N2  - 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.
KW  - adenosine
KW  - inosine
KW  - rheumatoid arthritis
KW  - osteoarthritis
KW  - synoviocytes
KW  - inflammation
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/62603
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-626032
SN  - 1422-0067
N1  - 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).
VL  - 22
IS  - 16, art. 8956
SP  - 1
EP  - 18
PB  - Molecular Diversity Preservation International
CY  - Basel
ER  -