Abstract
BackgroundTo 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).MethodsADAM-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.ResultsADAM-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.ConclusionsThese 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.
Highlights
To examine the expression of A disintegrin and metalloprotease family protein (ADAM)-17 in rheumatoid arthritis (RA) biological fluids and the role it plays in monocyte adhesion to RA fibroblast-like synoviocytes (FLSs)
To determine whether ADAM-17 was expressed in serum, we examined ADAM-17 levels in RA, OA, and NL sera using Enzyme-linked immunosorbent assay (ELISA)
ADAM-17 was not presented in OA synovial tissues. (This result indicates ADAM-17 might be involved in joint destruction.) We clearly demonstrated that ADAM-17 expression is higher in RA serum than NL serum and is related to disease activity
Summary
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). The pathogenesis of RA is only partially understood, inflammatory cells, macrophages, lymphocytes, and fibroblasts are known to produce several cytokines and chemokines in RA inflammation [2]. Anti-CD20 therapies which deplete B-cell and T-cell regulation therapies by binding cytotoxic lymphocyte antigen-4 are highly effective treatments for RA [6, 7]. These therapies have been shown to be effective in RA patients, they sometimes
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