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Evidence-Based Complementary and Alternative Medicine
Volume 2012, Article ID 746426, 8 pages
http://dx.doi.org/10.1155/2012/746426
Research Article

Inhibitory Effect of Curcumol on Jak2-STAT Signal Pathway Molecules of Fibroblast-Like Synoviocytes in Patients with Rheumatoid Arthritis

1Department of Traditional Chinese Medicine, Southwest Hospital, Third Military Medical University, Chongqing 400038, China
2Institute of Burn Research, State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital, Third Military Medical University, Chongqing 400038, China

Received 4 October 2011; Revised 21 December 2011; Accepted 23 December 2011

Academic Editor: Youn Chul Kim

Copyright © 2012 Heng Wang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Hyperplasia of synovial membrane in rheumatoid arthritis (RA) is a critical pathological foundation for inducing articular injury. The janus kinase and signal transducer and activator of transcription (Jak-STAT) pathway plays a critical role in synovial membrane proliferation induced by platelet-derived growth factor (PDGF). To explore the anti-cell proliferation mechanism of curcumol, a pure monomer extracted from Chinese medical plant zedoary rhizome, the changes of Jak2-STAT1/3 signal pathway-related molecules in synoviocytes were observed in vitro. In this study, the fibroblast-like synoviocytes (FLS) in patients with RA were collected and cultured. The following parameters were measured: cell proliferation (WST-1 assay), cell cycles (fluorescence-activated cell sorting, FACS), STAT1 and STAT3 activities (electrophoretic mobility shift assay, EMSA), and the protein expressions of phosphorylated Jak2, STAT1, and STAT3 (Western blot). It was shown that curcumol could inhibit the RA-FLS proliferation and DNA synthesis induced by PDGF-BB in a dose-dependent manner in vitro. The transcription factors activities of STAT1 and STAT3 were obviously elevated after PDGF-BB stimulation ( ). Super-shift experiments identified the STAT1 or STAT3 proteins in the complex. Furthermore, the different concentration curcumol could downregulate the DNA binding activities of STAT1 and STAT3 ( ) and inhibit the phosphorylation of Jak2 while it had no effect on the protein expressions of STAT1 and STAT3. Positive correlations were found between changes of cell proliferation and DNA-binding activities of STAT1 and STAT3, respectively ( ). In conclusion, curcumol might suppress the FLS proliferation and DNA synthesis induced by PDGF-BB through attenuating Jak2 phosphorylation, downregulating STAT1 and STAT3 DNA-binding activities, which could provide theoretical foundation for clinical treatment of RA.