ADAM-17 is expressed on rheumatoid arthritis fibroblast-like synoviocytes and regulates proinflammatory mediator expression and monocyte adhesion

• Published in: Arthritis Research & Therapy Vol. 20; no. 1; pp. 159 - 8
• Main Authors: Ishii, Sho, Isozaki, Takeo, Furuya, Hidekazu, Takeuchi, Hiroko, Tsubokura, Yumi, Inagaki, Katsunori, Kasama, Tsuyoshi
• Format: Journal Article
• Language: English
• Published: England Springer Science and Business Media LLC 02.08.2018; BioMed Central Ltd; BioMed Central; BMC
• Subjects: ADAM-17; ADAM17 Protein; Aged; Alzheimer's disease; Arthritis; Arthritis, Rheumatoid; Cancer therapies; Care and treatment; Cell adhesion; Cell adhesion & migration; Chemokines; Cytokines; Diseases of the musculoskeletal system; Enzymes; Female; Fibroblasts; Gene expression; Humans; Inflammation; Joint surgery; Male; Middle Aged; Monocytes; Pathogenesis; Proteins; R&D; RC925-935; Research & development; Research Article; Rheumatoid arthritis; Rodents; Synovial Membrane; Synoviocytes; Tumor necrosis factor-TNF; United States > US; ADAM-17; Cytokines; Rheumatoid arthritis; Cell adhesion
• ISSN: 1478-6362; 1478-6354; 1478-6362
• DOI: 10.1186/s13075-018-1657-1

To examine the expression of ADAM-17 in rheumatoid arthritis (RA) biological fluids and the role it plays in monocyte adhesion to RA fibroblast-like synoviocytes (FLSs). ADAM-17 expression was measured by enzyme-linked immunosorbent assays (ELISAs) in serum from normal (NL) subjects, osteoarthritis (OA) patients, and RA patients. We also analyzed the correlation between ADAM-17 and disease activity score 28 (DAS28) in RA. To determine expression of ADAM-17 in RA synovial tissues (STs) and RA FLS, we performed immunofluorescence analyses. To determine the role of ADAM-17 in RA, we transfected RA FLSs with small interfering RNA (siRNA) against ADAM-17. THP-1 adhesion to ADAM-17 siRNA-transfected RA FLSs was measured. Finally, adhesion molecules on ADAM-17 siRNA-transfected RA FLSs were measured using cell surface ELISAs. ADAM-17 in RA serum was significantly higher than that in NL and OA serum and correlated with DAS28. ADAM-17 in RA synovial fluids was higher than that in OA synovial fluids. ADAM-17 was expressed on RA cells lining STs and RA FLSs. THP-1 adhesion to ADAM-17 siRNA-transfected RA FLSs was decreased compared with that to control siRNA-transfected RA FLSs. ICAM-1 on TNF-α-stimulated ADAM-17 siRNA-transfected RA FLSs was significantly decreased compared with that on control siRNA-transfected RA FLSs. These data indicate that ADAM-17 is expressed on RA STs and plays a role in RA inflammation by regulating monocyte adhesion to RA FLSs. ADAM-17 might be an important inflammatory mediator in inflammatory diseases such as RA.