Anti-inflammatory signaling through G protein-coupled receptors

Ge, Yunjun; Liao, Qiwen; Xu, Yechun; Zhao, Qiang; Wu, Beili; Ye, Richard D.

doi:10.1038/s41401-020-00523-1

Cited by 23 publications

(17 citation statements)

References 53 publications

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“…While there are currently no experimentally determined structures, molecular docking of LXA 4 into the FPR2 structure suggests this molecule occupies a shallow binding pocket deep within the receptor core that differs from the binding site of the agonists in the experimentally determined structures (Ge, Liao, et al, 2020). Nonetheless, the binding pose partially overlaps the mid/C‐terminal‐region (YMV and MLF) of WKYMVm and fMLFII, forming interactions with a number of FPR2 residues that also interact with these peptides, including hydrogen bonding with D106 3.33 , R201 5.38 and R205 5.42 , and Van der Waal interactions with W254 6.48 .…”

Section: Structural Insights Into Agonist Engagement Of Fpr2mentioning

confidence: 99%

“…LXA 4 ) to generate FPR2 signalling (de Gaetano et al, 2019, 2021; Merlin et al, 2022). It is possible there is a disconnect between heterologous‐ versus endogenous‐expressed FPR2 or allosteric modes of receptor interaction (Ge, Liao, et al, 2020), that once fully explored in light of publication of FPR2 structure (Chen et al, 2020; Zhuang et al, 2020), may provide an explanation for these apparent discrepancies. At present, in the style of NC‐IUPHAR where single receptor nomenclature is preferred, based on confirmed phylogeny and activation by N‐ formylpeptides (albeit at higher concentrations), we refer to this receptor as FPR2 throughout the review.…”

Section: Introduction and Receptor Nomenclaturementioning

confidence: 99%

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Formylpeptide receptor 2: Nomenclature, structure, signalling and translational perspectives: IUPHAR review 35

Qin

Norling

Vecchio

et al. 2022

British J Pharmacology

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We discuss the fascinating pharmacology of formylpeptide receptor 2 (FPR2; often referred to as FPR2/ALX since it binds lipoxin A4). Initially identified as a low‐affinity ‘relative’ of FPR1, FPR2 presents complex and diverse biology. For instance, it is activated by several classes of agonists (from peptides to proteins and lipid mediators) and displays diverse expression patterns on myeloid cells as well as epithelial cells and endothelial cells, to name a few. Over the last decade, the pharmacology of FPR2 has progressed from being considered a weak chemotactic receptor to a master‐regulator of the resolution of inflammation, the second phase of the acute inflammatory response. We propose that exploitation of the biology of FPR2 offers innovative ways to rectify chronic inflammatory states and represents a viable avenue to develop novel therapies. Recent elucidation of FPR2 structure will facilitate development of the anti‐inflammatory and pro‐resolving drugs of next decade.

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Section: Structural Insights Into Agonist Engagement Of Fpr2mentioning

confidence: 99%

Section: Introduction and Receptor Nomenclaturementioning

confidence: 99%

Formylpeptide receptor 2: Nomenclature, structure, signalling and translational perspectives: IUPHAR review 35

Qin

Norling

Vecchio

et al. 2022

British J Pharmacology

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“…Despite the large numbers of SPMs, the actions of all the SPMs are thought to be mediated by only seven independent receptors (CHEMR23, BLT-1, LGR6, GPR37, GPR18, FPR2, and GPR32). 28,29 Only six are expressed in rodents for there is no GPR32 homolog. 30 Among these receptors, there appears to be significant ligand poly-pharmacology (single SPMs binding to more than one receptor) and receptor pleiotropy (single receptor activated by multiple ligands).…”

Section: Impact Statementmentioning

confidence: 99%

“…30 Among these receptors, there appears to be significant ligand poly-pharmacology (single SPMs binding to more than one receptor) and receptor pleiotropy (single receptor activated by multiple ligands). 28,29 Given the time that has elapsed since the discovery of SPMs and the importance of inflammation in so many bladder diseases, it is surprising that no studies have examined their therapeutic potential in the bladder. Previously, Monastyrskaya et al examined the expression of many annexin family members, including Annexin-A1, in the human bladder.…”

Section: Impact Statementmentioning

confidence: 99%

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Specialized pro-resolution mediators in the bladder: Receptor expression and recovery of bladder function from cystitis

Hughes

Allkanjari

Odom

et al. 2022

Exp Biol Med (Maywood)

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Inflammation is a central process in most benign bladder disorders, and its control is a delicate balance between initiating factors and resolving factors. While recent discoveries have shown a central role for the NLRP3 inflammasome in initiation, the resolving pathways remain unexplored. Resolution is controlled by specialized pro-resolution mediators (SPMs) functioning through seven receptors (six in rodents). Here we demonstrate expression of all seven in humans (six in mice) through immunocytochemistry. Expression was universal in urothelia with most also expressed in smooth muscle. We next explored the therapeutic potential of three SPMs; Resolvin E1 (RvE1), Maresin 1 (MaR1), and Protectin D1 (PD1). SPMs promote epithelial wound/barrier repair and RvE1 triggered dose-dependent wound closure in urothelia in vitro (scratch assay) (EC90 = 12.5 nM). MaR1 and PD1 were equally effective at this concentration. In vivo analyses employed a cyclophosphamide (CP) model of bladder inflammation (Day 0-CP [150 mg/kg], Day 1 to 3 SPM [25 µg/kg/day], Day 4 – analysis). All three SPMs reduced bladder inflammation (Evans blue) and bladder weights to control levels. Effects of RvE1 were also examined by urodynamics. CP decreased void volume, increased frequency and decreased bladder capacity while RvE1 restored values to control levels. Finally, SPMs reduce fibrosis and RvE1 reduced urothelial expression of TGF-β and collagen I to control values. Together these results expand the known SPMs active in the bladder tissue and provide promising therapeutic targets for controlling inflammation in a wide variety of inflammation-associated benign bladder diseases.

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The combined signatures of G protein-coupled receptor family and immune landscape provide a prognostic and therapeutic biomarker in endometrial carcinoma

Chen

Luo

Yang

et al. 2023

J Cancer Res Clin Oncol

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G protein-coupled receptors (GPRs) are one of the largest surface receptor superfamilies, and many of them play essential roles in biological processes, including immune responses. In this study, we aim to construct a GPR- and tumor immune environment (TME-i)-associated risk signature to predict the prognosis of patients with endometrial carcinoma (EC). The GPR score was generated by applying univariate Cox regression and the Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression in succession. This involved identifying the differentially expressed genes (DEGs) in the Cancer Genome Atlas-Uterine Corpus Endometrioid Carcinoma (TCGA-UCEC) cohort. Simultaneously, the CIBERSORT algorithm was applied to identify the protective immune cells for TME score construction. Subsequently, we combined the GPR and TME scores to establish a GPR-TME classifier for conducting clinical prognosis assessments. Various functional annotation algorithms were used to conduct biological process analysis distinguished by GPR-TME subgroups. Furthermore, weighted correlation network analysis (WGCNA) was applied to depict the tumor somatic mutations landscapes. Finally, we compared the immune-related molecules between GPR-TME subgroups and resorted to the Tumor Immune Dysfunction and Exclusion (TIDE) for immunotherapy response prediction. The mRNA and protein expression of GPR-related gene P2RY14 were, respectively, validated by RT-PCR in clinical samples and HPA database. To conclude, our GPR-TME classifier may aid in predicting the EC patients’ prognosis and immunotherapy responses.

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Anti-inflammatory signaling through G protein-coupled receptors

Cited by 23 publications

References 53 publications

Formylpeptide receptor 2: Nomenclature, structure, signalling and translational perspectives: IUPHAR review 35

Formylpeptide receptor 2: Nomenclature, structure, signalling and translational perspectives: IUPHAR review 35

Specialized pro-resolution mediators in the bladder: Receptor expression and recovery of bladder function from cystitis

The combined signatures of G protein-coupled receptor family and immune landscape provide a prognostic and therapeutic biomarker in endometrial carcinoma

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