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

Arthritis Res Ther. 2018 Aug 2;20(1):159. doi: 10.1186/s13075-018-1657-1.


Background: 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).

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: ADAM-17; Cell adhesion; Cytokines; Rheumatoid arthritis.

MeSH terms

  • ADAM17 Protein / metabolism*
  • Aged
  • Arthritis, Rheumatoid / metabolism*
  • Cell Adhesion / physiology
  • Cytokines / biosynthesis
  • Female
  • Fibroblasts / metabolism*
  • Humans
  • Male
  • Middle Aged
  • Monocytes / metabolism*
  • Synovial Membrane / metabolism
  • Synoviocytes / metabolism*


  • Cytokines
  • ADAM17 Protein
  • ADAM17 protein, human