ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1028

ADAM-10 Plays Monocyte Migration and Adhesion in Rheumatoid Arthritis Synovial Fibroblasts

Takeo Isozaki1,2, Sho Ishii2, Shinichiro Nishimi2, Airi Maeoka2, Mayu Saito2, Nao Oguro2, Shinya Seki2, Yoko Miura2, Yusuke Miwa2, Koei Oh3, Yoichi Toyoshima3, Masanori Nakamura3, Katsunori Inagaki3 and Tsuyoshi Kasama2, 1Internal Medicine, Division of Rheumatology, University of Michigan Medical Center, Ann Arbor, MI, 2Div of Rheumatology, Showa University School of Med, Shinagawa-ku Tokyo, Japan, 3Department of Orthopedics, Showa University School of Med, Tokyo, Japan

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: , , ,

Session Information

Title: Cytokines, Mediators, Cell-cell Adhesion, Cell Trafficking and Angiogenesis

Session Type: Abstract Submissions (ACR)

Background/Purpose :A disintegrin and metalloprotease family proteins (ADAMs) have been reported to be involved in a number of inflammatory conditions. We previously reported that ADAM-10 mediated rheumatoid arthritis (RA) angiogenesis. In this study, we examine the expression of ADAM-10 in RA biological fluids and the role it plays in monocyte migration, cell adhesion, and proliferation.

Methods :ADAM-10 expression was determined in serum and synovial fluids (SFs) from normal (NL) subjects, osteoarthritis (OA) patients and RA patients using enzyme linked immunosorbent assay (ELISA). To determine expression of ADAM-10 on RA synovial fibroblasts, immunofluorescence was performed. To examine the role of ADAM-10 in RA synovial fluids (SFs), we performed THP-1 (human acute monocytic leukemia cell line) chemotaxis. To block the expression of ADAM-10, RA synovial fibroblasts were transfected with siRNA against ADAM-10. In order to determine that ADAM-10 mediates monocyte adhesion, ADAM-10 siRNA transfected RA synovial fibroblast adhesion assay was performed. To determine if ADAM-10 played a role in cell proliferation in the RA synovium, ADAM-10 siRNA-transfected RA synovial fibroblast proliferation assays were performed.

Results :The expression of ADAM-10 in RA serum was significantly higher compared to NL serum [mean ± SE; 450 ± 44 pg/ml (n=90) and 85 ± 33 pg/ml (n=34), respectively] and was correlated with a disease activity score of 28. ADAM-10 concentration in RA SFs was significantly elevated compared with that in OA SFs [(727 ± 144 pg/ml (n=10) and 255 ± 42 pg/ml (n=7), respectively]. ADAM-10 was expressed on RA synovial tissue lining cells and synovial fibroblasts. ADAM-10-depleted RA SFs showed a 56 ± 9% (n=5 patients) decrease in THP-1 migratory activity compared to sham-depleted controls. Adhesion of THP-1 to ADAM-10 siRNA-transfected RA synovial fibroblasts in response to tumor necrosis factor (TNF)-α was significantly decreased compared with control siRNA-transfected RA synovial fibroblasts. Finally, RA synovial fibroblasts transfected with ADAM-10 siRNA showed less proliferation in response to TNF-α at 2.5 ng/ml for 48 hours.

Conclusion :These data indicate that ADAM-10 plays a role in monocyte migration in RA and suggest that targeting ADAM-10 may provide a method by which to decrease inflammation and potentially treat other inflammatory diseases.

Disclosure:

T. Isozaki,
None;

S. Ishii,
None;

S. Nishimi,
None;

A. Maeoka,
None;

M. Saito,
None;

N. Oguro,
None;

S. Seki,
None;

Y. Miura,
None;

Y. Miwa,

Tanabe-Mitsubishi,

2,

Wyeth Pharmaceuticals,

2,

Chugai,

2,

Abbott Immunology Pharmaceuticals,

2,

Asteras,

2,

Ono,

2,

Bristol-Myers Squibb,

2;

K. Oh,
None;

Y. Toyoshima,
None;

M. Nakamura,
None;

K. Inagaki,
None;

T. Kasama,
None.

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