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Nucleotide signalling during inflammation

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Abstract

Inflammatory conditions are associated with the extracellular release of nucleotides, particularly ATP. In the extracellular compartment, ATP predominantly functions as a signalling molecule through the activation of purinergic P2 receptors. Metabotropic P2Y receptors are G-protein-coupled, whereas ionotropic P2X receptors are ATP-gated ion channels. Here we discuss how signalling events through P2 receptors alter the outcomes of inflammatory or infectious diseases. Recent studies implicate a role for P2X/P2Y signalling in mounting appropriate inflammatory responses critical for host defence against invading pathogens or tumours. Conversely, P2X/P2Y signalling can promote chronic inflammation during ischaemia and reperfusion injury, inflammatory bowel disease or acute and chronic diseases of the lungs. Although nucleotide signalling has been used clinically in patients before, research indicates an expanding field of opportunities for specifically targeting individual P2 receptors for the treatment of inflammatory or infectious diseases.

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Figure 1: Extracellular nucleotide release and signalling during inflammation.
Figure 2: P2Y2R signalling during injury resolution and chronic inflammation.
Figure 3: P2X7R signalling during infection and inflammation.

Change history

  • 14 May 2014

    An incorrect URL was shown for http://www.clinicaltrials.gov/ in the print version of this Review, and has been corrected in the online version.

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Acknowledgements

We acknowledge S. A. Eltzschig for help with artwork during manuscript preparation. The present research is supported by Deutsche Forschungsgemeinschaft grant ID7/3-1 ID7/4-1 and a grant by the Boehringer-Ingelheim Foundation to I.D., as well as National Institutes of Health grants R01-DK097075, R01-HL0921, R01-DK083385, R01-HL098294, POIHL114457-01 and a grant by the Crohn’s and Colitis Foundation of America to H.K.E.

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M.I., D.F. and H.K.E. all contributed to the writing of this paper.

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Correspondence to Marco Idzko.

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Idzko, M., Ferrari, D. & Eltzschig, H. Nucleotide signalling during inflammation. Nature 509, 310–317 (2014). https://doi.org/10.1038/nature13085

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