J. Exp. Med.
© The Rockefeller University Press
0022-1007/97/03/975/06 $2.00
Volume 185, Number 5, March 3, 1997 975-980

BRIEF DEFINITIVE REPORT:
Presence of Cyclophilin A in Synovial Fluids of Patients with Rheumatoid Arthritis

By Andreas Billich,^* Gottfried Winkler,^* Heinrich Aschauer,^* Antal Rot,^* and Peter Peichl^*

From the ^* Sandoz Research Institute, A-1235 Vienna, and  Kaiser Franz Joseph Hospital, Department of Rheumatology, A-1100 Vienna, Austria

Cyclophilins have been suggested to act as leukocyte chemotactic factors produced in the course of inflammation. Therefore we looked for the presence of cyclophilins in the synovial fluids (SF) from patients with rheumatoid arthritis (RA). Peptidyl prolyl cis-trans isomerase activity (PPIase) was measured in SF from knee punctures of 26 patients with RA and five patients with knee osteoarthritis (OA). PPIase was detected in SF from RA patients, but not in samples from OA patients. Enzyme activity was sensitive to inhibition by cyclosporin A (IC₅₀ = 28-50 nM). Estimated concentrations of the SF-derived cyclophilin based on the enzyme activity were in the range of 11 to 705 nM. The presence of cyclophilin in the SF showed disease correlation; its concentration correlated with the number of cells in the SF (r   = 0.91, P <0.0001) and with the percentage of neutrophils in the cellular infiltrate and was higher in more acute cases of joint swelling. In immunoblots of partially purified preparations of SF from RA patients, an ~18-kD protein band reacted with polyclonal antibodies that recognize cyclophilin A and B, but not with antibodies specific for cyclophilin B. Sequencing of this protein revealed identity of the NH₂-terminal amino acids with those of human cyclophilin A. The finding is unexpected since cyclophilin B rather than A is generally regarded as the secreted isoform, the presence of cyclophilin A being confined to the cytoplasm. Our data support the hypothesis that cyclophilins may contribute to the pathogenesis of inflammatory diseases, possibly by acting as cytokines. This may offer a possible explanation of the effectiveness of cyclosporin A in RA, in addition to the known immunosuppressive effects of the drug.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Yang, Y., Lu, N., Zhou, J., Chen, Z.-n., Zhu, P. (2008). Cyclophilin A up-regulates MMP-9 expression and adhesion of monocytes/macrophages via CD147 signalling pathway in rheumatoid arthritis. Rheumatology (Oxford) 47: 1299-1310 [Abstract] [Full Text]  
• Satoh, K., Matoba, T., Suzuki, J., O'Dell, M. R., Nigro, P., Cui, Z., Mohan, A., Pan, S., Li, L., Jin, Z.-G., Yan, C., Abe, J.-i., Berk, B. C. (2008). Cyclophilin A Mediates Vascular Remodeling by Promoting Inflammation and Vascular Smooth Muscle Cell Proliferation. Circulation 117: 3088-3098 [Abstract] [Full Text]  
• Shamaei-Tousi, A., Halcox, J. P., Henderson, B. (2007). Stressing the obvious? Cell stress and cell stress proteins in cardiovascular disease. Cardiovasc Res 74: 19-28 [Abstract] [Full Text]  
• Catterall, J. B., Rowan, A. D., Sarsfield, S., Saklatvala, J., Wait, R., Cawston, T. E. (2006). Development of a novel 2D proteomics approach for the identification of proteins secreted by primary chondrocytes after stimulation by IL-1 and oncostatin M. Rheumatology (Oxford) 45: 1101-1109 [Abstract] [Full Text]  
• Arora, K., Gwinn, W. M., Bower, M. A., Watson, A., Okwumabua, I., MacDonald, H. R., Bukrinsky, M. I., Constant, S. L. (2005). Extracellular Cyclophilins Contribute to the Regulation of Inflammatory Responses. J. Immunol. 175: 517-522 [Abstract] [Full Text]  
• Jin, Z.-G., Lungu, A. O., Xie, L., Wang, M., Wong, C., Berk, B. C. (2004). Cyclophilin A Is a Proinflammatory Cytokine that Activates Endothelial Cells. Arterioscler. Thromb. Vasc. Bio. 24: 1186-1191 [Abstract] [Full Text]  
• Kim, S.-H., Lessner, S. M., Sakurai, Y., Galis, Z. S. (2004). Cyclophilin A as a Novel Biphasic Mediator of Endothelial Activation and Dysfunction. Am. J. Pathol. 164: 1567-1574 [Abstract] [Full Text]  
• Li, W., Liu, P, Pilcher, B., Anderson, R. (2001). Cell-specific targeting of caveolin-1 to caveolae, secretory vesicles, cytoplasm or mitochondria. J. Cell Sci. 114: 1397-1408 [Abstract]  
• Jin, Z.-G., Melaragno, M. G., Liao, D.-F., Yan, C., Haendeler, J., Suh, Y.-A., Lambeth, J. D., Berk, B. C. (2000). Cyclophilin A Is a Secreted Growth Factor Induced by Oxidative Stress. Circ. Res. 87: 789-796 [Abstract] [Full Text]  
• Liao, D.-F., Jin, Z.-G., Baas, A. S., Daum, G., Gygi, S. P., Aebersold, R., Berk, B. C. (2000). Purification and Identification of Secreted Oxidative Stress-induced Factors from Vascular Smooth Muscle Cells. J. Biol. Chem. 275: 189-196 [Abstract] [Full Text]  
• Kullertz, G., Luthe, S., Fischer, G. (1998). Semiautomated microtiter plate assay for monitoring peptidylprolyl cis/trans isomerase activity in normal and pathological human sera. Clin. Chem. 44: 502-508 [Abstract] [Full Text]  
• Sherry, B., Zybarth, G., Alfano, M., Dubrovsky, L., Mitchell, R., Rich, D., Ulrich, P., Bucala, R., Cerami, A., Bukrinsky, M. (1998). Role of cyclophilin A in the uptake of HIV-1 by macrophages and T lymphocytes. Proc. Natl. Acad. Sci. USA 95: 1758-1763 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS