Sohn, Rebecca and Junker, Marius and Meurer, Andrea and Zaucke, Frank and Straub, Rainer H. and Jenei-Lanzl, Zsuzsa (2021) Anti-Inflammatory Effects of Endogenously Released Adenosine in Synovial Cells of Osteoarthritis and Rheumatoid Arthritis Patients. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 22 (16): 8956. ISSN , 1422-0067
Full text not available from this repository. (Request a copy)Abstract
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(1), A(2A), A(2B) and A(3)) 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(2A)AR agonist CGS 21680 significantly inhibited IL-6 and induced TNF and IL-10 only in RA, while the A(2B)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(2A)- and A(2B)AR. Stimulating CD39/CD73 with simultaneous ADA blockage in addition to TNF inhibition might represent a promising therapeutic strategy.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | LOW-GRADE INFLAMMATION; DEAMINASE LEVELS; RECEPTOR; FLUID; CYTOKINES; CLASSIFICATION; PATHOGENESIS; AGONISTS; THERAPY; PATHWAY; adenosine; inosine; rheumatoid arthritis; osteoarthritis; synoviocytes; inflammation |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 13 Sep 2022 13:53 |
| Last Modified: | 13 Sep 2022 13:53 |
| URI: | https://pred.uni-regensburg.de/id/eprint/47341 |
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