Contribution of Cyclophilin A to the Regulation of Inflammatory Processes in Rheumatoid Arthritis
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Previous studies show that cyclophilin A (CypA) acts as a strong chemotactic cytokine to neutrophils, eosinophils, and monocytes in rheumatoid arthritis (RA).
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.
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).
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.
KeywordsCyclophilin A rheumatoid arthritis monocytes
List of abbreviations
polymerase chain reaction
cytometric bead array
tumor necrosis factor α
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).
The authors declare that they have no competing interests.
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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