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Abstract Number: 960

ADAM-17 Is Expressed on Rheumatoid Arthritis Synovial Fibroblasts and Mediates Monocyte Migration and Adhesion

Sho Ishii, Takeo Isozaki, Airi Nishimi, Shinichiro Nishimi, Takahiro Tokunaga, Hidekazu Furuya, Kuninobu Wakabayashi and Tsuyoshi Kasama, Div of Rheumatology, Showa University School of Med, Shinagawa-ku Tokyo, Japan

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: Adhesion molecules, cytokines, Fibroblasts, monocytes and rheumatoid arthritis (RA)

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Session Information

Date: Monday, November 6, 2017

Title: Cytokines, Mediators, Cell-Cell Adhesion, Cell Trafficking and Angiogenesis Poster II: Mesenchymal Cells Do React - But How?

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose: A disintegrin and metalloproteinase 17 (ADAM-17), also known as tumor necrosis factor-α converting enzyme (TACE), have been reported to be involved in a number of inflammatory conditions. We examined the expression of ADAM-17 in rheumatoid arthritis (RA) biological fluids and the role it plays in monocyte migration and adhesion to RA synovial fibroblasts.

Methods: ADAM-17 expression was measured by enzyme-linked immunosorbent assay in serum and synovial fluids from normal (NL) subjects, osteoarthritis (OA) patients and RA patients. We also analyzed relativity with ADAM-17 and disease activity score 28 (DAS28) in RA. To determine expression of ADAM-17 on RA synovial tissues (STs) and RA fibroblast like synoviocite (FLS), immunofluorescence was performed. To determine the role of ADAM-17 in RA, RA FLSs or THP-1(human acute monocytic leukemia cell line) were transfected with small interfering RNA (siRNA) against of ADAM-17. THP-1 adhesion to ADAM-17 siRNA transfected RA FLSs was measured. THP-1 chemotaxis assay was performed towards RA synovial fluids or monocyte chemotactic protein-1 (MCP-1)/CCL2.

Results: The levels of ADAM-17 in RA serum was significantly higher compared with NL serum [mean ± SE; 2093 ± 539 pg/ml (n=23) and 0 ± 0 pg/ml (n=7), respectively, p<0.05] . ADAM-17 in RA synovial fluids was higher compared with OA synovial fluids [1644 ± 952 pg/ml (n=10) and 4.6 ± 4.3 pg/ml (n=7), respectively, p<0.05] .The level of ADAM-17 in RA serum was also correlated with DAS28 (n=58, r=0.64, p<0.05). ADAM-17 was expesssed on RA ST lining cells. On the other hand, ADAM-17 was not expressed on OA STs. ADAM-17 was also expressed on RA FLS. THP-1 adhesion to ADAM-17 siRNA transfected RA FLS had decreased compared with that to control siRNA transfected RA FLS [adhesion index; 0.61 ± 0.10 (n=12) and 0.93 ± 0.05 (n=12), respectively, p<0.05]. We found ADAM-17 siRNA transfected THP-1 cells had decreased migration compared with control siRNA transfected THP-1 cells towards RA synovial fluids [number of THP-1 migrated 6 ± 2 (n=6) and 33 ± 12 (n=6), respectively, p<0.05]. Furthermore, ADAM-17 siRNA transfected THP-1 cells also had decreased migration compared with control siRNA transfected THP-1 cells towards MCP-1/CCL2 [number of THP-1 migrated 27 ± 4 (n=3) and 146 ± 18 (n=3), respectively, p<0.05].

Conclusion: These data indicate that ADAM-17 may play a role in RA inflammation by regulating monocyte migration and adhesion to RA synovial fibroblasts. ADAM-17 may be a potential target in inflammatory disease like RA.


Disclosure: S. Ishii, None; T. Isozaki, None; A. Nishimi, None; S. Nishimi, None; T. Tokunaga, None; H. Furuya, None; K. Wakabayashi, None; T. Kasama, None.

To cite this abstract in AMA style:

Ishii S, Isozaki T, Nishimi A, Nishimi S, Tokunaga T, Furuya H, Wakabayashi K, Kasama T. ADAM-17 Is Expressed on Rheumatoid Arthritis Synovial Fibroblasts and Mediates Monocyte Migration and Adhesion [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/adam-17-is-expressed-on-rheumatoid-arthritis-synovial-fibroblasts-and-mediates-monocyte-migration-and-adhesion/. Accessed .
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