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

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.

Implications of ADAM17 activation for hyperglycaemia, obesity and type 2 diabetes

“…As you will discover in this review, ADAM17 has both beneficial and detrimental effects. Although it has been shown to be beneficial for embryonic development, liver health and adipocyte differentiation, it is also implicated in the pathogenesis of many different diseases including, but not limited to cancer [ 19 ], heart disease [ 20 ], diabetes [ 21 , 22 ], rheumatoid arthritis [ 23 ] and Alzheimer’s disease [ 24 ]. In this review, we aim to highlight the impact of ADAM17 on the progression of Metabolic Syndrome.…”

Genetic Correlation Analysis and Transcriptome-wide Association Study Suggest the Overlapped Genetic Mechanism between Gout and Attention-deficit Hyperactivity Disorder

“…42 ADAM17 is associated with various diseases including polycystic kidney disease, Alzheimer disease and autoimmune diseases such as rheumatoid arthritis (RA). 43 ADAM17 is expressed on RA synovial tissues and fibroblast-like synoviocytes and is associated with disease activity in RA. 43 ADAM17 substrate glycoprotein VI is critical for platelet microparticle formation involved in the inflammation that is important for hemostasis, thrombosis, cancer, and inflammation.…”

<p>ADAM17 Genetic Variants and the Response of TNF-α Inhibitor in Rheumatoid Arthritis Patients</p>

“…20,21 TACE expressions were up-regulated in rheumatoid arthritis patients and TACE was shown to be an important regulator of the secretion of TNF-α in previous studies. 22,23 Among the small number of studies examining the relationship between ADAM17 and pharmacotherapy, Umemura et al reported that suppression of ADAM17 can be a crucial therapeutic target in the treatment of abatacept in patients with rheumatoid arthritis. 24 Another study showed that ADAM17 haplotype was associated with a clinical response to infliximab in Crohn's disease patients.…”