title: Human articular chondrocytes express ChemR23 and chemerin; ChemR23 promotes inflammatory signalling upon binding the ligand chemerin(21-157).
abstract: BACKGROUND
  Chemerin is a chemotactic peptide which directs leukocytes expressing the chemokine-like receptor ChemR23 towards sites of inflammation. ChemR23 is a G protein-coupled receptor which binds several different ligands, and it is also expressed by other cell types such as adipocytes. In addition to chemotaxis, recent reports suggest that ChemR23 is capable of mediating either inflammatory or anti-inflammatory effects, depending on the type of ligand it binds. In the present study, we aimed to clarify whether human chondrocytes express ChemR23 and chemerin, and whether chemerin/ChemR23 signalling could affect secretion of inflammatory mediators.
  
  
  METHODS
  Tissue sections were taken from human knee joints and labelled with antibodies towards chemerin and ChemR23. Chondrocytes from cartilage tissue were isolated, cultured and assessed for chemerin and ChemR23 expression by PCR and immunolabelling. Receptor activation and intracellular signalling were studied by assessment of phosphorylated mitogen activated protein kinases (MAPKs) and phosphorylated Akt after stimulating cells with recombinant chemerin(21-157). Biological effects of chemerin(21-157) were investigated by measuring secretion of pro-inflammatory cytokines and metalloproteases in cell supernatants.
  
  
  RESULTS
  Both serially cultured human articular chondrocytes and resident cells in native cartilage expressed chemerin and ChemR23. Stimulating cells with chemerin(21-157) resulted in phosphorylation of p44/p42 MAPKs (ERK 1/2) and Akt (Ser 473). Also, significantly enhanced levels of the pro-inflammatory cytokines interleukin-6 (IL-6), interleukin-8 (IL-8), tumour necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), and the matrix metalloproteases MMP-1, MMP-2, MMP-3, MMP-8 and MMP-13 were detected.
  
  
  CONCLUSIONS
  These results demonstrate that human chondrocytes express both the receptor ChemR23 and the ligand chemerin. Chemerin(21-157) stimulation engaged signal-transduction pathways that further promoted inflammatory signalling in chondrocytes, as judged by an enhanced secretion of cytokines and metalloproteases. Taken together, the previously reported chemotaxis and the present findings suggest that the receptor and its ligand may play pivotal roles in joint inflammation.
authors.affiliation: Department of Laboratory Medicine, University Hospital of North Norway, Sykehusveien 38, N-9038, Tromsø, Norway.
authors.forename: Vivian
authors.initials: V
authors.lastname: Berg
authors.forename: Baldur
authors.initials: B
authors.lastname: Sveinbjörnsson
authors.forename: Signy
authors.initials: S
authors.lastname: Bendiksen
authors.forename: Jan
authors.initials: J
authors.lastname: Brox
authors.forename: Khaled
authors.initials: K
authors.lastname: Meknas
authors.forename: Yngve
authors.initials: Y
authors.lastname: Figenschau
mesh_terms: D015153:Blotting, Western; D002358:Cartilage, Articular / Q000276:immunology / Q000378:metabolism*; D018925:Chemokines / Q000276:immunology / Q000378:metabolism*; D019902:Chondrocytes / Q000276:immunology / Q000378:metabolism*; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins; D007719:Knee Joint / Q000276:immunology / Q000378:metabolism; D019707:Receptors, Chemokine / Q000276:immunology / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology
chemical_list: C102741:CMKLR1 protein, human; D018925:Chemokines; D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; C478630:RARRES2 protein, human; D019707:Receptors, Chemokine