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

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          Abstract

          We discuss the fascinating pharmacology of formylpeptide receptor 2 (FPR2; often referred to as FPR2/ALX since it binds lipoxin A 4). 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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          Most cited references185

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          Damage-Associated Molecular Patterns in Inflammatory Diseases

          Damage-associated molecular patterns (DAMPs) are endogenous danger molecules that are released from damaged or dying cells and activate the innate immune system by interacting with pattern recognition receptors (PRRs). Although DAMPs contribute to the host's defense, they promote pathological inflammatory responses. Recent studies have suggested that various DAMPs, such as high-mobility group box 1 (HMGB1), S100 proteins, and heat shock proteins (HSPs), are increased and considered to have a pathogenic role in inflammatory diseases. Here, we review current research on the role of DAMPs in inflammatory diseases, including rheumatoid arthritis, systemic lupus erythematosus, osteoarthritis, atherosclerosis, Alzheimer's disease, Parkinson's disease, and cancer. We also discuss the possibility of DAMPs as biomarkers and therapeutic targets for these diseases.
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            Novel Markers to Delineate Murine M1 and M2 Macrophages

            Classically (M1) and alternatively activated (M2) macrophages exhibit distinct phenotypes and functions. It has been difficult to dissect macrophage phenotypes in vivo, where a spectrum of macrophage phenotypes exists, and also in vitro, where low or non-selective M2 marker protein expression is observed. To provide a foundation for the complexity of in vivo macrophage phenotypes, we performed a comprehensive analysis of the transcriptional signature of murine M0, M1 and M2 macrophages and identified genes common or exclusive to either subset. We validated by real-time PCR an M1-exclusive pattern of expression for CD38, G-protein coupled receptor 18 (Gpr18) and Formyl peptide receptor 2 (Fpr2) whereas Early growth response protein 2 (Egr2) and c-Myc were M2-exclusive. We further confirmed these data by flow cytometry and show that M1 and M2 macrophages can be distinguished by their relative expression of CD38 and Egr2. Egr2 labeled more M2 macrophages (~70%) than the canonical M2 macrophage marker Arginase-1, which labels 24% of M2 macrophages. Conversely, CD38 labeled most (71%) in vitro M1 macrophages. In vivo, a similar CD38+ population greatly increased after LPS exposure. Overall, this work defines exclusive and common M1 and M2 signatures and provides novel and improved tools to distinguish M1 and M2 murine macrophages.
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              THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: G protein-coupled receptors.

              The Concise Guide to PHARMACOLOGY 2021/22 is the fifth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of nearly 1900 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes over 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/bph.15538. G protein-coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2021, and supersedes data presented in the 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.
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                Author and article information

                Contributors
                m.perretti@qmul.ac.uk
                rebecca.ritchie@monash.edu
                Journal
                Br J Pharmacol
                Br J Pharmacol
                10.1111/(ISSN)1476-5381
                BPH
                British Journal of Pharmacology
                John Wiley and Sons Inc. (Hoboken )
                0007-1188
                1476-5381
                29 July 2022
                October 2022
                29 July 2022
                : 179
                : 19 ( doiID: 10.1111/bph.v179.19 )
                : 4617-4639
                Affiliations
                [ 1 ] Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences Monash University Melbourne Victoria Australia
                [ 2 ] William Harvey Research Institute, Barts and the London School of Medicine Queen Mary University of London London UK
                [ 3 ] Diabetes Complications Research Centre, Conway Institute and School of Medicine University College Dublin Dublin Ireland
                Author notes
                [*] [* ] Correspondence

                Rebecca H. Ritchie, Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University (Parkville Campus), 381 Royal Parade, Parkville, VIC 3052, Australia.

                Email: rebecca.ritchie@ 123456monash.edu

                Mauro Perretti, The William Harvey Research Institute, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UK.

                Email: m.perretti@ 123456qmul.ac.uk

                Author information
                https://orcid.org/0000-0003-2169-2686
                https://orcid.org/0000-0002-4412-1707
                https://orcid.org/0000-0003-2068-3331
                https://orcid.org/0000-0002-8610-0058
                Article
                BPH15919
                10.1111/bph.15919
                9545948
                35797341
                02b3d1f1-88ee-40d0-822b-dd64a1e8d658
                © 2022 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 22 May 2022
                : 10 November 2021
                : 09 June 2022
                Page count
                Figures: 2, Tables: 2, Pages: 23, Words: 24578
                Funding
                Funded by: Medical Research Council , doi 10.13039/501100007155;
                Award ID: MR/N017544/1
                Funded by: National Heart Foundation of Australia , doi 10.13039/501100001030;
                Award ID: 101857
                Award ID: 102787
                Funded by: Versus Arthritis , doi 10.13039/501100012041;
                Award ID: 22235
                Funded by: Science Foundation Ireland , doi 10.13039/501100001602;
                Award ID: SFI/15/US B3130
                Funded by: Bristol‐Myers Squibb , doi 10.13039/100002491;
                Funded by: Barts Charity , doi 10.13039/100015652;
                Award ID: MGU0443
                Award ID: MGU0489
                Funded by: National Health and Medical Research Council (NHMRC) of Australia
                Award ID: ID1120853
                Award ID: ID1145769
                Award ID: ID1155302
                Award ID: ID1187989
                Categories
                Invited Review
                Invited Review
                Custom metadata
                2.0
                October 2022
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.2.0 mode:remove_FC converted:07.10.2022

                Pharmacology & Pharmaceutical medicine
                alxr,annexin‐a1,fpr,lipoxin a4 , n‐formylated peptides,resolution of inflammation

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