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Upregulation of Kallistatin Expression in Rheumatoid Joints

CHRONG-REEN WANG, SHIH-YAO CHEN, AI-LI SHIAU, CHAO-LIANG WU, I-MING JOU, LEE CHAO, and JULIE CHAO

ABSTRACT.

Objective.
Previous studies demonstrated suppression of rat ankle arthritis by local injection of kallistatin gene, a negative regulator of angiogenesis. We analyzed circulating levels, synovial concentrations, and tissue localizations of kallistatin in patients with rheumatoid arthritis (RA).

Methods. Paired plasma and joint fluid samples were simultaneously obtained from 24 patients with RA and 14 with osteoarthritis (OA). Synovial tissues from 5 patients with RA and 5 with OA were obtained during surgery. Fibroblast-like synoviocytes (FLS) and mononuclear cells (MNC) were prepared. ELISA was used to measure kallistatin levels of plasma, joint fluid, cell lysate, and synovium homogenate extract. Synovial tissues were subjected to Western blot and immunohistochemical staining. In addition, the tissue kallikrein (TK) levels of plasma and joint fluid samples were also measured by the ELISA.

Results. Circulating and synovial levels of kallistatin and TK were elevated in patients with RA. The immunohistochemical assay exhibited stainings of kallistatin on both infiltrating MNC and FLS. Intracellular kallistatin levels were significantly elevated in MNC and FLS from patients with RA.

Conclusion. Elevated kallistatin levels were demonstrated in patients with RA, particularly in synovial tissues, FLS, and MNC. This report is the first to demonstrate upregulation of kallistatin expression in rheumatoid joints. (First Release Oct 15 2007; J Rheumatol 2007;34:2171-6)

Key Indexing Terms:

KALLISTATIN
RHEUMATOID ARTHRITIS
ANGIOGENESIS


From the College of Medicine, National Cheng Kung University, Tainan, Taiwan; and the Medical University of South Carolina, Charleston, South Carolina, USA.

Supported by NSC 94-2314-B-006-052 and NSC 95-2314-B-006-010 from the National Science Council, Taiwan, and by NIH HL-44083 from the National Institutes of Health, USA.

C-R. Wang, MD, PhD, Associate Professor, Section of Rheumatology and Immunology, Department of Internal Medicine; S-Y. Chen, MS, Institute of Basic Medical Sciences; A-L. Shiau, PhD, Department of Microbiology and Immunology; C-L. Wu, PhD, Department of Biochemistry and Molecular Biology; I-M. Jou, MD, Department of Orthopedics, College of Medicine, National Cheng Kung University; L. Chao, PhD; J. Chao, PhD, Department of Biochemistry and Molecular Biology, Medical University of South Carolina.

Address reprint requests to Dr. C-R. Wang, Section of Rheumatology and Immunology, Department of Internal Medicine, No. 1 University Road, Tainan, 701, Taiwan – Republic of China. E-mail: wangcr@mail.ncku.edu.tw

Accepted for publication July 27, 2007.




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