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Journal of Clinical Immunology

, Volume 30, Issue 1, pp 24–33 | Cite as

Contribution of Cyclophilin A to the Regulation of Inflammatory Processes in Rheumatoid Arthritis

  • Li Wang
  • Cong-hua Wang
  • Jun-feng Jia
  • Xiao-kui Ma
  • Yu Li
  • Hong-bin Zhu
  • Hao Tang
  • Zhi-nan Chen
  • Ping Zhu
Article

Abstract

Introduction

Previous studies show that cyclophilin A (CypA) acts as a strong chemotactic cytokine to neutrophils, eosinophils, and monocytes in rheumatoid arthritis (RA).

Methods

In this study, monocytes were stimulated by purified CypA and the production of matrix metalloproteinase (MMPs), the cell invasion and the release of inflammatory cytokines were detected respectively by gelatin zymography, invasion assay, and cytometric bead array FCM.

Results

The elevated level of inflammatory cytokine IL-8 was also detected. Results showed that CypA significantly promoted the invasion of THP-1 cells and increased the production of MMP-2 and MMP-9, which displayed a biphasic concentration dependency. In vivo experiments found that the cartilage erosion scores in CypA injection group were significantly higher than those in control group (P < 0.05).

Conclusion

Our findings suggest that CypA significantly enhances the secretion of MMP-2 and MMP-9, the cell invasion, and the inflammatory cytokines production of monocytes. Our findings may shed some new light on the inflammatory process and the degradation of cartilage and bone in RA.

Keywords

Cyclophilin A rheumatoid arthritis monocytes 

List of abbreviations

CypA

cyclophilin A

CsA

cyclosporine A

MMP

matrix metalloproteinase

PCR

polymerase chain reaction

IPTG

Isopropyl-β-d-thiogalactopyranoside

Ni–NTA

Ni-nitrilotriacetic acid

FMLP

N-Formyl-Met-Leu-Phe

CBA

cytometric bead array

LPS

lipopolysaccharide

PMB

polymyxin B

TNF-α

tumor necrosis factor α

IL

interleukin

RA

rheumatoid arthritis

Notes

Acknowledgements

This work was supported by the Key Program of the National Natural Science Foundation of China under Grant (No. 30530720) and the National Basic Research Program (No. 2009CB521705).

Competing interests

The authors declare that they have no competing interests.

Authors’ contributions

LW participated in the design of the study and drafted the manuscript. CW, one of the co-first authors, conducted the chemotaxis, invasion, gel zymography, and CBA assays; performed the statistical analysis and helped to draft the manuscript. JJ constructed the animal model and performed in vivo assays. XM and YL participated in the construction of the expression vector and the induction of the CypA protein. HZ and HT performed the purification of the CypA. ZC and PZ, the corresponding authors, participated in the design of the study and helped to draft the manuscript. All authors read and approved the final manuscript.

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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Li Wang
    • 1
  • Cong-hua Wang
    • 1
  • Jun-feng Jia
    • 1
  • Xiao-kui Ma
    • 2
  • Yu Li
    • 2
  • Hong-bin Zhu
    • 2
  • Hao Tang
    • 2
  • Zhi-nan Chen
    • 2
  • Ping Zhu
    • 1
  1. 1.Department of Clinical Immunology, State Key Discipline of Cell Biology, Xijing HospitalFourth Military Medical UniversityXi’anPeople’s Republic of China
  2. 2.Department of Cell Biology/Cell Engineering Research Centre, Cancer Biology of State Key Laboratory and State Key Discipline of Cell BiologyFourth Military Medical UniversityXi’anPeople’s Republic of China

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