Purinergic receptors and the inflammatory response mediated by lipids

The inflammatory response is regulated by the production of different extracellular mediators, including lipids and extracellular nucleotides. In the extracellular environment, intermediate lipids activate specific G-protein-coupled receptors (GPCRs) in target cells and promote cell recruitment and activation. Extracellular nucleotides activate two types of receptors, the ionotropic purinergic P2X and the metabotropic purinergic P2Y receptors, inducing the release of cytokines and promoting cell recruitment. Several P2X receptors are associated with an increase in the production of immunoactive lipids mediators, which in turn are able to interfere with the activation of different P2Y receptors, establishing a tight signalling link between purinergic receptors and lipid mediators. In this review, we summarise recent studies indicating signalling crosstalk between purinergic P2X and P2Y receptor activation and lipid mediators with a focus on inflammatory diseases. Novel concepts arising from this crosstalk would result in the development of combinatorial therapies targeting lipid synthesis together with individual P2 receptors for the management of inflammatory diseases.