P1 receptors and cytokine secretion |
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Authors: | Maria P Abbracchio Stefania Ceruti |
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Institution: | (1) Laboratory of Molecular and Cellular Pharmacology of Purinergic Transmission, Department of Pharmacological Sciences, University of Milan, Via Balzaretti, 9, 20133 Milan, Italy |
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Abstract: | Evidence has accumulated in the last three decades to suggest tissue protection and regeneration by adenosine in multiple
different cell types. Adenosine produced in hypoxic or inflamed environments reduces tissue injury and promotes repair by
receptor-mediated mechanisms. Among other actions, regulation of cytokine production and secretion by immune cells, astrocytes
and microglia (the brain immunocytes) has emerged as a main mechanism at the basis of adenosine effects in diseases characterized
by a marked inflammatory component. Many recent studies have highlighted that signalling through A1 and A2A adenosine receptors can powerfully prevent the release of pro-inflammatory cytokines, thus inhibiting inflammation and reperfusion
injury. However, the activation of adenosine receptors is not invariably protective of tissues, as signalling through the
A2B adenosine receptor has been linked to pro-inflammatory actions which are, at least in part, mediated by increased release
of pro-inflammatory cytokines from epithelial cells, astrocytes and fibroblasts. Here, we discuss the multiple actions of
P1 receptors on cytokine secretion, by analyzing, in particular, the role of the various adenosine receptor subtypes, the
complex reciprocal interplay between the adenosine and the cytokine systems, their pathophysiological significance and the
potential of adenosine receptor ligands as new anti-inflammatory agents. |
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Keywords: | adenosine asthma central nervous system chronic heart failure cytokines immune cells inflammation |
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