 |
|
|
 |
RUHANGIZ T. KILANI, WALTER P. MAKSYMOWYCH, ALASTAIR AITKEN, GILLES BOIRE, YVES ST-PIERRE, YUNYUAN LI, and AZIZ GHAHARY
ABSTRACT. Methods. In general, 2 sets of synovial and serum samples were analyzed. The first set of 17 SF samples from patients with inflamed joints were analyzed for 14-3-3 h isoform by Western blot. The second set of 12 matching serum and SF samples were analyzed for 14-3-3 h, g, MMP-1, and MMP-3 by the same procedure. The MMP-1 stimulatory effect of various concentrations of 14-3-3 h in cultured fibroblasts was then evaluated. Results. We found that of the seven 14-3-3 isoforms tested (ß, g, e, h, s, q, and z), the levels of only 2 isoforms, h and g, were easily detectable in SF samples from patients with inflammatory joint diseases. The levels of these proteins were significantly higher in inflammatory SF and serum samples relative to controls. The values of these proteins correlated strongly with the levels of MMP-1 and MMP-3, 2 biomarkers for rheumatoid arthritis, detected in sera. Further, the level of 14-3-3 h was significantly higher in a pool of 12 serum samples from patients with inflammatory joint disease than those from healthy individuals. Conclusion. Detection of only 2 (14-3-3 h and g) out of 7 different isoforms in SF suggests they are specific to the site of inflammation, and that distinguishes them from barely detectable levels of these isoforms found in normal serum. The MMP-1 stimulatory effect of the h isoform explains its correlation with MMP-1 levels seen in these samples. (First Release July 1 2007; J Rheumatol 2007;34:1650-7) Key Indexing Terms:
PROTEINS 14-3-3
From the Department of Surgery, University of British Columbia, Vancouver, British Columbia, Canada. Supported by the Canadian Institute of Health Research (NSM 66119) and in part by the Canadian Arthritis Network. Prof. Maksymowych is a Senior Scholar of the Alberta Heritage Foundation for Medical Research. R.T. Kilani, PhD; A. Ghahary, PhD, BC Professioonal Fire Fighters' Burn and Wound Healing Research Lab, Department of Surgery, University of British Columbia, Vancouver, British Columbia; W.P. Maksymowych, FRCP; Y. Li, MD, PhD, Department of Medicine, University of Alberta, Edmonton, Alberta; A. Aitken, PhD, School of Biological Sciences, the University of Edinburgh, Edinburgh, UK; G. Boire, MD, Department of Medicine, Division of Rheumatology, University of Sherbrooke, Sherbrooke, Quebec; Y. St-Pierre, PhD, INRS-Institut-Armand-Frappier, University of Quebec, Laval, Quebec. Address reprint requests to A. Ghahary, 351-2660 Oak Street, Jack Bell Research Centre, Vancouver, BC V6H 3Z6, Canada. E-mail: aghahary@interchange.ubc.ca Accepted for publication April 25, 2007. |
