P2X1 and P2X3 Purinergic Receptors Differentially Modulate the Inflammatory Response in Human Osteoarthritic Synovial Fibroblasts

摘要

Background/Aims P2X receptors are membrane ion channels activated by extracellular adenosine 5’-triphosphate (ATP) which contribute to various physiological processes. The present study describes in synovial fibroblasts (SFs) obtained from osteoarthritis (OA) patients and in SW 982 cells derived from human synovial sarcoma a pharmacological characterization of P2Xsub1/sub and P2Xsub3/sub receptors implicated in the modulation of inflammatory processes in joint diseases. Methods mRNA, western blotting, saturation and competition binding experiments were used to characterize purinergic receptors. From a functional point of view nuclear factor ?B (NF-?B) activation, tumour necrosis factor-α (TNF-α), interleukin 6 (IL-6) and prostaglandin Esub2/sub (PGEsub2/sub) production were evaluated by means of enzyme-linked immunosorbent assays. Results P2Xsub1/sub and P2Xsub3/sub receptors were present with high affinity and density. Selected purinergic agonists and antagonists exhibited a different thermodynamic behavior. P2Xsub1/sub receptors showed an anti-inflammatory effect reducing NF-?B activation and TNF-α release whilst P2Xsub3/sub receptors mediated opposite response. No effect was mediated by P2Xsub1/sub and P2Xsub3/sub receptors on IL-6 and PGEsub2/sub production. Conclusion SFs from OA patients and SW 982 cells similarly express P2Xsub1/sub and P2Xsub3/sub receptors which are able to modulate in opposite way some functional responses closely associated with inflammation suggesting that purinergic receptors may represent a potential target in therapeutic anti-inflammatory joint interventions.