Adenosine analogs and electromagnetic fields inhibit prostaglandin E2 release in bovine synovial fibroblasts

被引:70
作者
De Mattei, M. [1 ]
Varani, K. [2 ]
Masieri, F. F. [1 ]
Pellati, A. [1 ]
Ongaro, A. [1 ]
Fini, M. [3 ]
Cadossi, R. [4 ]
Vincenzi, F.
Borea, P. A. [2 ]
Caruso, A. [1 ]
机构
[1] Univ Ferrara, Dept Morphol & Embryol, I-44100 Ferrara, Italy
[2] Univ Ferrara, Dept Clin & Expt Med, I-44100 Ferrara, Italy
[3] Inst Orthoped, Res Inst Codivilla Putti Rizzoli, Dept Expt Surg, Bologna, Italy
[4] Igea Biophys Lab, Carpi, Italy
关键词
Adenosine receptors; Synovial fibroblasts; Electromagnetic field; PGE(2); ARTICULAR-CARTILAGE EXPLANTS; INFLAMMATORY JOINT DISEASE; RHEUMATOID-ARTHRITIS; IN-VITRO; HUMAN NEUTROPHILS; PROTEOGLYCAN SYNTHESIS; RECEPTOR ACTIVATION; MEDICAL-MANAGEMENT; SEPTIC ARTHROSIS; GENE-EXPRESSION;
D O I
10.1016/j.joca.2008.06.002
中图分类号
R826.8 [整形外科学]; R782.2 [口腔颌面部整形外科学]; R726.2 [小儿整形外科学]; R62 [整形外科学(修复外科学)];
学科分类号
摘要
Objective: To investigate the role of adenosine analogs and electromagnetic field (EMF) stimulation on prostaglandin E-2 (PGE(2)) release and cyclooxygenase-2 (COX-2) expression in bovine synovial fibroblasts (SFs). Methods: SFs isolated from synovia were cultured in monolayer. Saturation and binding experiments were performed by using typical adenosine agonists: N6-cyclohexyladenosine (CHA, A(1)), 2-[p-(2-carboxyethyl)-phenetyl-amino]-5'-N-ethylcarboxamidoadenosine (CGS 21680, A(2A)), 5'-N-ethylcarboxamidoadenosine (NECA, non-selective), N6-(3-iodobenzyl)2-chloroadenosine-5'-N-methyluronamide (CI-IB-MECA, A(3)). SFs were treated with TNF-alpha (10 ng/ml) and lipopolysaccharide (LPS) (1 mu g/ml) to activate inflammatory response. Adenosine analogs were added to control and TNF-alpha- or LPS-treated cultures both in the absence and in the presence of adenosine deaminase (ADA) which is used to deplete endogenous adenosine. Parallel cultures were exposed to EMFs (75 Hz, 1-5 mT) during the period in culture (24 h). PGE(2) release was measured by immunoassay. COX-2 expression was evaluated by RT-PCR. Results: TNF-alpha and LPS stimulated PGE(2) release. All adenosine agonists, except for CI-IB-MECA, significantly inhibited PGE(2) production. EMFs inhibited PGE(2) production in the absence of adenosine agonists and increased the effects of CHA, CGS 21680 and NECA. In ADA, the inhibition on PGE(2) release induced by CHA, CGS and NECA was stronger than in the absence of ADA and the EMF-inhibitory effect was lost. Changes in PGE(2) levels were associated to modification of COX-2 expression. Conclusions: This study supports anti-inflammatory activities of A(1) and A(2A) adenosine receptors and EMFs in bovine SFs. EMF activity appears mediated by an EMF-induced up-regulation of A(2A) receptors. Biophysical and/or pharmacological modulation of adenosine pathways may play an important role to control joint inflammation. (C) 2008 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:252 / 262
页数:11
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