P2X(1) and P2X(3) purinergic receptors differentially modulate the inflammatory response in human osteoarthritic synovial fibroblasts.

Varani, Katia, De Mattei, Monica, Vincenzi, Fabrizio, Tosi, Alice, Targa, Martina, Masieri, Federica, Pellati, Agnese, Massari, Leo and Borea, Pier Andrea (2010) P2X(1) and P2X(3) purinergic receptors differentially modulate the inflammatory response in human osteoarthritic synovial fibroblasts. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology, 25 (2-3). pp. 325-36. ISSN 1421-9778

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Abstract

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 P2X(1) and P2X(3) 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 kappaB (NF-kappaB) activation, tumour necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6) and prostaglandin E(2) (PGE(2)) production were evaluated by means of enzyme-linked immunosorbent assays.

RESULTS

P2X(1) and P2X(3) receptors were present with high affinity and density. Selected purinergic agonists and antagonists exhibited a different thermodynamic behavior. P2X(1) receptors showed an anti-inflammatory effect reducing NF-kappaB activation and TNF-alpha release whilst P2X(3) receptors mediated opposite response. No effect was mediated by P2X(1) and P2X(3) receptors on IL-6 and PGE(2) production.

CONCLUSION

SFs from OA patients and SW 982 cells similarly express P2X(1) and P2X(3) 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.

Item Type: Article
Uncontrolled Keywords: P2X purinergic receptors, Osteoarthritis, Human synovial fibroblasts, TNF-α production, PGE2 and IL-6 release
Subjects: Q Science > Q Science (General)
Q Science > QP Physiology
R Medicine > R Medicine (General)
Divisions: Faculty of Health & Science > Department of Science & Technology
Depositing User: Federica Masieri
Date Deposited: 23 Feb 2021 09:58
Last Modified: 01 Mar 2021 16:05
URI: http://oars.uos.ac.uk/id/eprint/1629

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