Anti-inflammatory signaling through G protein-coupled receptors

Abstract

G protein-coupled receptors (GPCRs) play important roles in human physiology. GPCRs are involved in immunoregulation including regulation of the inflammatory response. Chemotaxis of phagocytes and lymphocytes is mediated to a great extent by the GPCRs for chemoattractants including myriads of chemokines. Accumulation and activation of phagocytes at the site of inflammation contribute to local inflammatory response. A handful of GPCRs have been found to transduce anti-inflammatory signals that promote resolution of inflammation. These GPCRs interact with selected metabolites of arachdonic acid, such as lipoxins, and of omega-3 essential fatty acids, such as resolvins and protectins. Despite mounting evidence for the in vivo functions of these anti-inflammatory and pro-resolving ligands paired with their respective GPCRs, the underlying signaling mechanisms have not been fully delineated. The present review summarizes what we have learned about these GPCRs, their structures and signaling pathways and the prospect of targeting these receptors for novel anti-inflammatory therapies.

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Fig. 1: Signaling pathways of FPR2 activated by proinflammatory ligands.
Fig. 2: Anti-inflammatory and pro-resolving signaling through dimerized FPR2.
Fig. 3: Energy landscape changes induced by ATL binding to FPR2.
Fig. 4: Overall structure of the FPR2-LXA4 complex.
Fig. 5: Mode of FPR2 binding to the LXA4 ligand.

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Acknowledgements

This work was supported in part by grants from the Fundo para o Desenvolvimento das Ciências e da Tecnologia (FDCT 072/2015/A2) and from the University of Macau (MYRG2016-00246-ICMS-QRCM). YJG and RDY were supported by the President Fund of the Chinese University of Hong Kong, Shenzhen. QWL was supported by the Ganghong Young Scholar Development Fund.

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Correspondence to Richard D. Ye.

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Ge, Yj., Liao, Qw., Xu, Yc. et al. Anti-inflammatory signaling through G protein-coupled receptors. Acta Pharmacol Sin 41, 1531–1538 (2020). https://doi.org/10.1038/s41401-020-00523-1

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