Upregulation of kallistatin expression in rheumatoid joints.
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.


CONCLUSIONS
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.
Wang
Chrong-Reen
CR
Section of Rheumatology and Immunology, Department of Internal Medicine, College of Medicine, National Cheng Kung University, No. 1 University Road, Tainan, Taiwan. wangcr@mail.ncku.edu.tw
Chen
Shih-Yao
SY
Shiau
Ai-Li
AL
Wu
Chao-Liang
CL
Jou
I-Ming
IM
Chao
Lee
L
Chao
Julie
J
D000328:Adult; D000368:Aged; D000818:Animals; D001169:Arthritis, Experimental / Q000628:therapy; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000378:metabolism*; D005260:Female; D015316:Genetic Therapy; D006801:Humans; D007610:Kallikreins / Q000097:blood / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D010003:Osteoarthritis / Q000097:blood / Q000378:metabolism; D051381:Rats; D015843:Serpins / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D013582:Synovial Fluid / Q000378:metabolism; D015854:Up-Regulation
D015843:Serpins; C051324:kallistatin; D007610:Kallikreins