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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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© The Author 2009. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Inhibitory effect of CD147/HAb18 monoclonal antibody on cartilage erosion and synovitis in the SCID mouse model for rheumatoid arthritis

Junfeng Jia1, Conghua Wang1, Zhanguo Shi1, Jingkang Zhao1, Yun Jia1, Zheng Zhao-Hui1, Xiaoyan Li1, Zhinan Chen2,* and Ping Zhu1,*

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, Xi’an, 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, Xi’an 710032, Shaanxi Province, P.R. of China. E-mail: zhuping{at}fmmu.edu.cn


   Abstract

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-{alpha} 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-{alpha} mAb, and in the mice treated with anti-CD147 mAb plus anti-TNF-{alpha} 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-{alpha}, 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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