PMID- 21192818
OWN - NLM
STAT- MEDLINE
DCOM- 20110623
LR  - 20220330
IS  - 1478-6362 (Electronic)
IS  - 1478-6354 (Print)
IS  - 1478-6354 (Linking)
VI  - 12
IP  - 6
DP  - 2010
TI  - Human articular chondrocytes express ChemR23 and chemerin; ChemR23 promotes 
      inflammatory signalling upon binding the ligand chemerin(21-157).
PG  - R228
LID - 10.1186/ar3215 [doi]
AB  - INTRODUCTION: 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-alpha), interleukin-1 beta (IL-1beta), 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.
FAU - Berg, Vivian
AU  - Berg V
AD  - Department of Laboratory Medicine, University Hospital of North Norway, 
      Sykehusveien 38, N-9038, Tromso, Norway.
FAU - Sveinbjornsson, Baldur
AU  - Sveinbjornsson B
FAU - Bendiksen, Signy
AU  - Bendiksen S
FAU - Brox, Jan
AU  - Brox J
FAU - Meknas, Khaled
AU  - Meknas K
FAU - Figenschau, Yngve
AU  - Figenschau Y
LA  - eng
PT  - Journal Article
DEP - 20101230
PL  - England
TA  - Arthritis Res Ther
JT  - Arthritis research & therapy
JID - 101154438
RN  - 0 (CMKLR1 protein, human)
RN  - 0 (Chemokines)
RN  - 0 (Cytokines)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (RARRES2 protein, human)
RN  - 0 (Receptors, Chemokine)
SB  - IM
CIN - Arthritis Res Ther. 2011;13(2):104. PMID: 21542878
MH  - Blotting, Western
MH  - Cartilage, Articular/immunology/*metabolism
MH  - Chemokines/immunology/*metabolism
MH  - Chondrocytes/immunology/*metabolism
MH  - Cytokines/biosynthesis/immunology
MH  - Humans
MH  - Immunohistochemistry
MH  - Inflammation/immunology/*metabolism
MH  - Intercellular Signaling Peptides and Proteins
MH  - Knee Joint/immunology/metabolism
MH  - Receptors, Chemokine/immunology/*metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Signal Transduction/immunology
PMC - PMC3046541
EDAT- 2011/01/05 06:00
MHDA- 2011/06/24 06:00
PMCR- 2010/12/30
CRDT- 2011/01/04 06:00
PHST- 2010/06/11 00:00 [received]
PHST- 2010/10/19 00:00 [revised]
PHST- 2010/12/30 00:00 [accepted]
PHST- 2011/01/04 06:00 [entrez]
PHST- 2011/01/05 06:00 [pubmed]
PHST- 2011/06/24 06:00 [medline]
PHST- 2010/12/30 00:00 [pmc-release]
AID - ar3215 [pii]
AID - 10.1186/ar3215 [doi]
PST - ppublish
SO  - Arthritis Res Ther. 2010;12(6):R228. doi: 10.1186/ar3215. Epub 2010 Dec 30.