title: ChemR23, the receptor for chemerin and resolvin E1, is expressed and functional on M1 but not on M2 macrophages.
abstract: ChemR23 is a G protein-coupled receptor that is triggered by two ligands, the peptide chemerin and the eicosapentaenoic acid-derived lipid mediator resolvin E1 (RvE1). Chemerin acts as a chemoattractant for monocytes and macrophages, whereas RvE1 promotes resolution of inflammation-inducing macrophage phagocytosis of apoptotic neutrophils. Although ChemR23-mediated signaling plays a role in mononuclear cell migration to inflamed tissue, as well as in the resolution of inflammation, its regulation in different polarization states of macrophages is largely unknown. We analyzed the expression and function of ChemR23 in monocytes and differently activated human primary macrophages. Using 5' RACE, we identified three transcription start sites and several splice variants of ChemR23 in both monocytes and macrophages. Although the promoters P1 and P3 are used equally in unpolarized macrophages, stimulation with LPS or IFN-γ leads to increased transcription from P3 in inflammatory M1 macrophages. Such ChemR23-expressing M1 macrophages are chemotactic to chemerin, whereas M2 macrophages not expressing ChemR23 surface receptor are not. Repolarization of ChemR23-expressing M1 macrophages with 10 nM RvE1 increases IL-10 transcription and phagocytosis of microbial particles, leading to a resolution-type macrophage distinct from the M2 phenotype. These results show that ChemR23 is tightly regulated in response to inflammatory and anti-inflammatory stimuli. The restricted expression of ChemR23 in naive and M1 macrophages supports the role of ChemR23 in the attraction of macrophages to inflamed tissue by chemerin and in the initiation of resolution of inflammation through RvE1-mediated repolarization of human M1 macrophages toward resolution-type macrophages.
authors: Division of Clinical Chemistry and Biochemistry, University Children's Hospital Zurich, CH-8032 Zurich, Switzerland; Children's Research Center, University Children's Hospital Zurich, CH-8032 Zurich, Switzerland; and Center for Integrative Human Physiology, University of Zurich, CH-8057 Zurich, Switzerland.
authors: Magdalena
authors: M
authors: Herová
authors: Division of Clinical Chemistry and Biochemistry, University Children's Hospital Zurich, CH-8032 Zurich, Switzerland; Children's Research Center, University Children's Hospital Zurich, CH-8032 Zurich, Switzerland; and Center for Integrative Human Physiology, University of Zurich, CH-8057 Zurich, Switzerland.
authors: Mattia
authors: M
authors: Schmid
authors: Division of Clinical Chemistry and Biochemistry, University Children's Hospital Zurich, CH-8032 Zurich, Switzerland; Children's Research Center, University Children's Hospital Zurich, CH-8032 Zurich, Switzerland; and Center for Integrative Human Physiology, University of Zurich, CH-8057 Zurich, Switzerland.
authors: Claudio
authors: C
authors: Gemperle
authors: Division of Clinical Chemistry and Biochemistry, University Children's Hospital Zurich, CH-8032 Zurich, Switzerland; Children's Research Center, University Children's Hospital Zurich, CH-8032 Zurich, Switzerland; and Center for Integrative Human Physiology, University of Zurich, CH-8057 Zurich, Switzerland martin.hersberger@kispi.uzh.ch.
authors: Martin
authors: M
authors: Hersberger
mesh_terms: D017398:Alternative Splicing; D018925:Chemokines / Q000235:genetics / Q000276:immunology*; D015118:Eicosapentaenoic Acid / Q000031:analogs & derivatives* / Q000276:immunology; D005786:Gene Expression Regulation; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007371:Interferon-gamma / Q000494:pharmacology; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D009928:Organ Specificity; D061251:Primary Cell Culture; D011401:Promoter Regions, Genetic; D019707:Receptors, Chemokine / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction; D024363:Transcription Initiation Site
chemical_list: C102741:CMKLR1 protein, human; D018925:Chemokines; C508609:IL10 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; C478630:RARRES2 protein, human; D019707:Receptors, Chemokine; D016753:Interleukin-10; D007371:Interferon-gamma; D015118:Eicosapentaenoic Acid; C499823:5S,12R,18R-trihydroxy-6Z,8E,10E,14Z,16E-eicosapentaenoic acid