title: Electromagnetic fields (EMFs) and adenosine receptors modulate prostaglandin E(2)  and cytokine release in human osteoarthritic synovial fibroblasts.
abstract: Synovial fibroblasts (SFs) contribute to the development of osteoarthritis (OA) by the secretion of a wide range of pro-inflammatory mediators, including cytokines and lipid mediators of inflammation. Previous studies suggest that electromagnetic fields (EMFs) may represent a potential therapeutic approach to limit cartilage degradation and control inflammation associated to OA, and that they may act through the adenosine pathway. Therefore, we investigated whether EMFs might modulate inflammatory activities of human SFs from OA patients (OASFs) treated with interleukin-1β (IL-1β), and the possible involvement of adenosine receptors (ARs) in mediating EMF effects. EMF exposure induced a selective increase in A(2A) and A(3) ARs. These increases were associated to changes in cAMP levels, indicating that ARs were functionally active also in EMF-exposed cells. Functional data obtained in the presence of selective A(2A) and A(3) adenosine agonists and antagonists showed that EMFs inhibit the release of prostaglandin E(2) (PGE(2)) and the proinflammatory cytokines interleukin-6 (IL-6) and interleukin-8 (IL-8), while stimulating the release of interleukin-10 (IL-10), an antinflammatory cytokine. These effects seem to be mediated by the EMF-induced upregulation of A(2A) and A(3) ARs. No effects of EMFs or ARs have been observed on matrix degrading enzyme production. In conclusion, this study shows that EMFs display anti-inflammatory effects in human OASFs, and that these EMF-induced effects are in part mediated by the adenosine pathway, specifically by the A(2A) and A(3) AR activation. Taken together, these results open new clinical perspectives to the control of inflammation associated to joint diseases.
authors.affiliation: Department of Morphology and Embryology, University of Ferrara, Ferrara, Italy. ngrlss@unife.it
authors.forename: A
authors.initials: A
authors.lastname: Ongaro
authors.forename: K
authors.initials: K
authors.lastname: Varani
authors.forename: F F
authors.initials: FF
authors.lastname: Masieri
authors.forename: A
authors.initials: A
authors.lastname: Pellati
authors.forename: L
authors.initials: L
authors.lastname: Massari
authors.forename: R
authors.initials: R
authors.lastname: Cadossi
authors.forename: F
authors.initials: F
authors.lastname: Vincenzi
authors.forename: P A
authors.initials: PA
authors.lastname: Borea
authors.forename: M
authors.initials: M
authors.lastname: Fini
authors.forename: A
authors.initials: A
authors.lastname: Caruso
authors.forename: M
authors.initials: M
authors.lastname: De Mattei
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004574:Electromagnetic Fields; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D016753:Interleukin-10 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008875:Middle Aged; D015207:Osteoarthritis, Hip / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D058906:Purinergic P1 Receptor Agonists / Q000494:pharmacology; D058915:Purinergic P1 Receptor Antagonists / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D043705:Receptor, Adenosine A2A / Q000378:metabolism; D043684:Receptor, Adenosine A3 / Q000378:metabolism; D018047:Receptors, Purinergic P1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D013583:Synovial Membrane / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
chemical_list: C508606:CXCL8 protein, human; D016207:Cytokines; C508609:IL10 protein, human; C508600:IL6 protein, human; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D012333:RNA, Messenger; D043705:Receptor, Adenosine A2A; D043684:Receptor, Adenosine A3; D018047:Receptors, Purinergic P1; D016753:Interleukin-10; D000242:Cyclic AMP; D051722:ADAM Proteins; D020782:Matrix Metalloproteinases; D015232:Dinoprostone