Expression and functional role of adenosine receptors in regulating inflammatory responses in human synoviocytes.

Varani, K, Vincenzi, F, Tosi, A, Targa, M, Masieri, Federica, Ongaro, A, De Mattei, M, Massari, L and Borea, P A (2010) Expression and functional role of adenosine receptors in regulating inflammatory responses in human synoviocytes. British journal of pharmacology, 160 (1). pp. 101-15. ISSN 1476-5381

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Abstract

BACKGROUND AND PURPOSE

Adenosine is an endogenous modulator, interacting with four G-protein coupled receptors (A(1), A(2A), A(2B) and A(3)) and acts as a potent inhibitor of inflammatory processes in several tissues. So far, the functional effects modulated by adenosine receptors on human synoviocytes have not been investigated in detail. We evaluated mRNA, the protein levels, the functional role of adenosine receptors and their pharmacological modulation in human synoviocytes.

EXPERIMENTAL APPROACH

mRNA, Western blotting, saturation and competition binding experiments, cyclic AMP, p38 mitogen-activated protein kinases (MAPKs) and nuclear factor (NF)-kappaB activation, tumour necrosis factor alpha (TNF-alpha) and interleukin-8 (IL-8) release were assessed in human synoviocytes isolated from patients with osteoarthritis.

KEY RESULTS

mRNA and protein for A(1), A(2A), A(2B) and A(3) adenosine receptors are expressed in human synoviocytes. Standard adenosine agonists and antagonists showed affinity values in the nanomolar range and were coupled to stimulation or inhibition of adenylyl cyclase. Activation of A(2A) and A(3) adenosine receptors inhibited p38 MAPK and NF-kappaB pathways, an effect abolished by selective adenosine antagonists. A(2A) and A(3) receptor agonists decreased TNF-alpha and IL-8 production. The phosphoinositide 3-kinase or G(s) pathways were involved in the functional responses of A(3) or A(2A) adenosine receptors. Synoviocyte A(1) and A(2B) adenosine receptors were not implicated in the inflammatory process whereas stimulation of A(2A) and A(3) adenosine receptors was closely associated with a down-regulation of the inflammatory status.

CONCLUSIONS AND IMPLICATIONS

These results indicate that A(2A) and A(3) adenosine receptors may represent a potential target in therapeutic modulation of joint inflammation.

Item Type: Article
Uncontrolled Keywords: adenosine receptors, human synoviocytes, mRNA, Western blotting, receptor binding, cAMP, MAPK, p38, NF‐κB, TNF‐α, IL‐8
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 10:04
Last Modified: 01 Mar 2021 16:05
URI: http://oars.uos.ac.uk/id/eprint/1628

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