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.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/adam-17-is-expressed-on-rheumatoid-arthritis-synovial-fibroblasts-and-mediates-monocyte-migration-and-adhesion/