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 e...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-08-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/22/16/8956 |
| Summary: | 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 (A<sub>1</sub>, A<sub>2A</sub>, A<sub>2B</sub> and A<sub>3</sub>) 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 A<sub>2A</sub>AR agonist CGS 21680 significantly inhibited IL-6 and induced TNF and IL-10 only in RA, while the A<sub>2B</sub>AR 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 A<sub>2A</sub>- and A<sub>2B</sub>AR. Stimulating CD39/CD73 with simultaneous ADA blockage in addition to TNF inhibition might represent a promising therapeutic strategy. |
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| ISSN: | 1661-6596 1422-0067 |