Contribution of cyclophilin A to the regulation of inflammatory processes in rheumatoid arthritis.
BACKGROUND
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).


CONCLUSIONS
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.
Wang
Li
L
Department of Clinical Immunology, State Key Discipline of Cell Biology, Xijing Hospital, Fourth Military Medical University, Shaanxi Province, People's Republic of China.
Wang
Cong-hua
CH
Jia
Jun-feng
JF
Ma
Xiao-kui
XK
Li
Yu
Y
Zhu
Hong-bin
HB
Tang
Hao
H
Chen
Zhi-nan
ZN
Zhu
Ping
P
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D021984:Cyclophilin A / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D007249:Inflammation; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D051379:Mice; D016513:Mice, SCID; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
D016207:Cytokines; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D021984:Cyclophilin A