4.6 Article

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

Journal

JOURNAL OF CLINICAL IMMUNOLOGY
Volume 30, Issue 1, Pages 24-33

Publisher

SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s10875-009-9329-1

Keywords

Cyclophilin A; rheumatoid arthritis; monocytes

Categories

Funding

  1. National Natural Science Foundation of China [30530720]
  2. National Basic Research Program [2009CB521705]

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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.

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