Rheumatology Advance Access originally published online on May 8, 2009
Rheumatology 2009 48(7):721-726; doi:10.1093/rheumatology/kep099
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Inhibitory effect of CD147/HAb18 monoclonal antibody on cartilage erosion and synovitis in the SCID mouse model for rheumatoid arthritis
1Department of Clinical Immunology, State Key Discipline of Cell Biology, Xijing Hospital, Fourth Military Medical University and 2Department of Cell Biology/Cell Engineering Research Centre, Cancer Biology of State Key Laboratory, State Key Discipline of Cell Biology, Fourth Military Medical University, Xian, Shaanxi Province, P. R. of China.
Correspondence to: Ping Zhu, Department of Clinical Immunology, State Key Discipline of Cell Biology, Xijing Hospital, Fourth Military Medical University, Xian 710032, Shaanxi Province, P.R. of China. E-mail: zhuping{at}fmmu.edu.cn
| Abstract |
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Objective. To explore the therapeutic potential of CD147/HAb18 mAb in the treatment of RA in severe combined immunodeficiency (SCID) mice engrafted with human cartilage and rheumatoid synovium tissue (SCID-HuRAg).
Methods. SCID-HuRAg mice were treated separately with CD147/HAb18 mAb, anti-TNF-
mAb or a combination of both. The mice in control group were treated with anti-Japanese encephalitis virus mAb. The volume of engrafts was measured and the number of inflammatory cells and cartilage erosion score were examined. Expression of MMP-2, -3 and -9 was determined by immunohistochemistry. Human inflammatory cytokine levels in mouse sera were assessed using cytometric bead array kit.
Results. The volume of engrafts decreased significantly in SCID-HuRAg mice treated separately with anti-CD147 mAb or anti-TNF-
mAb, and in the mice treated with anti-CD147 mAb plus anti-TNF-
mAb (P < 0.05). Significant reduction was observed in cartilage erosion score in anti-CD147 treatment group and combined treatment group (P < 0.05). Immunohistochemical analysis showed that expression of MMP-2, -3 and -9 was lower in the anti-CD147 treatment group and combined treatment group than in the control mAb group (P < 0.05). Moreover, the level of TNF-
, IL-6 and -8 in CD147 mAb group showed a significant decrease compared with that of the control mAb group (P < 0.05).
Conclusions. CD147/HAb18 mAb can reduce cartilage erosion and synovitis by inhibition of the MMPs and reduction of inflammatory cytokines in SCID-HuRAg mice, which suggests that CD147/HAb18 mAb is a promising treatment option for RA patients.
KEY WORDS: Rheumatoid arthritis, CD147, HAb18, Inflammation, SCID-HuRAg mouse, Pathology
*Ping Zhu and Zhinan Chen equally contributed to this work.
Submitted 27 October 2008;
revised version accepted 26 March 2009.
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