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Adenosine increases LPS ‐induced nuclear factor kappa B activation in smooth muscle cells via an intracellular mechanism and modulates it via actions on adenosine receptors
Author(s) -
Yang J.,
Zheng X.,
Haugen F.,
Darè E.,
Lövdahl C.,
Schulte G.,
Fredholm B. B.,
Valen G.
Publication year - 2014
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/apha.12176
Subject(s) - adenosine , adenosine a3 receptor , purinergic signalling , adenosine a2b receptor , adenosine a1 receptor , adenosine deaminase , adenosine receptor , chemistry , intracellular , receptor , medicine , nfkb1 , microbiology and biotechnology , endocrinology , biology , transcription factor , biochemistry , agonist , gene
Aim In inflamed and damaged cardiovascular tissues, local extracellular adenosine concentrations increase coincidentally with activation of the transcription factor nuclear factor kappa B ( NF κB). To investigate whether adenosine influences NF κB activation in vascular smooth muscle cells ( VSMC s) and, if so, to examine the role of its receptors. Methods VSMC s were isolated from NF κB–luciferase reporter mice, cultured and then treated by lipopolysaccharide ( LPS ) to activate NF κB signalling. Adenosine, adenosine receptor agonists and antagonists, adenosine deaminase and uptake inhibitors were used together with LPS to evaluate the role of adenosine and its receptors on NF κB activation, which was assessed by luciferase activity and NF κB target gene expression. Results Adenosine potentiated LPS ‐induced NF κB activation. This was dependent on adenosine uptake and enhanced by an adenosine deaminase inhibitor, suggesting that intracellular adenosine plays an important role. Non‐selective adenosine receptor agonists (2Cl‐Ado and NECA ) inhibited NF κB activation induced by LPS . Selective A 1 or A 2A antagonist given alone could not completely antagonize the NECA effect, indicating that the inhibitory effect was due to multiple adenosine receptors. The activation of the A 3 receptor further increased LPS ‐induced NF κB activation. Conclusions Adenosine increases LPS ‐induced nuclear factor kappa B activation in smooth muscle cells via an intracellular mechanism and decreases it via actions on A 1 and A 2A receptors. These results provide novel insights into the role of adenosine as a regulator of inflammation‐induced NF κB activation.