Monocyte chemoattractant protein-4 (MCP-4)/CCL13 is highly expressed in cartilage from patients with rheumatoid arthritis.
OBJECTIVE
To study the role of monocyte chemoattractant protein-4 (MCP-4)/CCL13 in the pathogenesis of rheumatoid arthritis (RA), we analysed the expression of MCP-4/CCL13 in chondrocytes, synovial fluid and serum from patients with RA and investigated the effect of MCP-4/CCL13 on the proliferation of synovial cells.


METHODS
Human articular cartilage specimens were obtained from joints from RA and osteoarthritis (OA) patients and normal joints (controls). Transcript levels of MCP-4 in cartilage were determined by real-time polymerase chain reaction. Protein levels were measured by enzyme-linked immunoassay. Cultured fibroblast-like synoviocytes (FLS) were treated with various concentrations of recombinant MCP-4/CCL13 protein, and cell proliferation was evaluated with a viability assay.


RESULTS
The gene expression of MCP-4 was significantly higher in cartilage from RA patients than in that from OA patients (P = 0.00902) and in normal cartilage (P = 0.00902). The concentration of MCP-4/CCL13 protein in serum from RA patients (mean 94.7 +/- 37.6 pg/ml) was significantly higher than in serum from OA patients (mean 49.2 +/- 31.2 pg/ml, P = 0.0051) and controls (mean 32.6 +/- 23.9 pg/ml, P = 0.0001). The concentration of MCP-4/CCL13 protein in synovial fluid from RA patients (mean 247.2 +/- 161.2 pg/ml) was also significantly higher than in that from OA patients (mean 29.6 +/- 50.5 pg/ml, P = 0.000019). Moreover, MCP-4/CCL13 enhanced the proliferation of FLS in a dose-dependent manner.


CONCLUSIONS
MCP-4/CCL13 is highly expressed in RA joints at the mRNA and protein levels. Our results suggest that MCP-4/CCL13 is secreted from chondrocytes and activates the proliferation of rheumatoid synovial cells, thereby leading to joint destruction in RA.
Iwamoto
T
T
Institute of Rheumatology, Tokyo Women's Medical University, 10-22 Kawada-cho, Shinjuku, Tokyo 162-0054, Japan.
Okamoto
H
H
Iikuni
N
N
Takeuchi
M
M
Toyama
Y
Y
Tomatsu
T
T
Kamatani
N
N
Momohara
S
S
D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D002358:Cartilage, Articular / Q000737:chemistry*; D002455:Cell Division; D002478:Cells, Cultured; D019902:Chondrocytes / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D005260:Female; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D018945:Monocyte Chemoattractant Proteins / Q000032:analysis* / Q000097:blood / Q000235:genetics; D020370:Osteoarthritis, Knee / Q000378:metabolism*; D054388:Receptors, CCR; D054397:Receptors, CCR3; D019707:Receptors, Chemokine / Q000032:analysis; D011994:Recombinant Proteins / Q000494:pharmacology; D013582:Synovial Fluid / Q000737:chemistry; D013583:Synovial Membrane / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology
C408223:ACKR4 protein, human; C099677:CCL13 protein, human; C515350:CCR3 protein, human; D018945:Monocyte Chemoattractant Proteins; D054388:Receptors, CCR; D054397:Receptors, CCR3; D019707:Receptors, Chemokine; D011994:Recombinant Proteins