The Effects Of Nuclear Factor-Kappa B Antisense Oligodeoxynucleotides On Chemotactic Function Of Peripheral Blood Mononuclear Cells From Patients With Rheumatoid Arthritis

Objective Rheumatoid arthritis(RA) is an autoimmune disease which is characterized by infiltrition of inflammatory cell and proliferating of synovium, progressive destruction of joint cartilage and bone. Increasing evidence shows that nuclear factor-kappa B(NF-κB) is activated in RA, but the primary cause of RA is unknow.The activation of peripheral blood lymphocytes, chronic inflammation in the joints, the production of cytokines, autoantibody and functional disability have been made in understanding pathogenesis. NF-κB play a key role in the pathogenesis of RA .Inhibition of NF-κB can become a new way to treat RA, and to screen new anti-rheumatic drugs. NF-κB antisense oligodeoxynucleotides is a new effective way to inhibit activity of nuclear factor-kappa B. This study was designed to illuminate the chemotactic function of peripheral blood mononuclear cells (PBMC) from patients with RA, and the effects of nuclear factor-kappa B antisense oligonucleotides on chemotactic function of PBMC from patients with RA,explain the molecular anti-rheumatic mechanism of nuclear factor-kappa B antisense oligodeoxynucleotides. Method 30 active RA patients fulfiled criteria by American College of Rheumatology and 10 healthy donors were involved in this study as control, PBMC from patients with RA were isolated and cultured in RPMI-1640 with antisense oligodeoxynucleotides, missense oligodeoxynucleotides and dexamethasone as controls, respectively, at the same time, chemoattractants such as IL-2, synovial fluid from patients with RA, and culture medium of primary cultured synoviocyte from patients with RA were put in adjacent bore, incubated in agarose gel with 5% CO2 for 3h, the chemotaxis distance was measured on microscope.Results 1.Elevated migration activity of PBMC from patients with RA compared to the normal controls without chemokines (P<0.05).2.Elevated chemotactic function of PBMC from patients RA to IL-2, synovial fluid from patients with RA, culture medium of primary cultured synoviocyte compared to the negtive controls(P<0.05).3.Significant decrease of chemotactic responses of PBMC from patients with RA by antisense oligdeoxynucleotides and dexamethasone compared to the PBMC from patients with RA by missense oligodeoxynucleotides and patients with RA controls(P<0.05).4. Decreased time-dependent chemotactic responses of PBMC to synovial fluid from paitents from RA.Conclusions 1. PBMC from patients with RA have more chemotactic activity. 2.Increased chemotactic function of PBMC from patients with RA was found and PBMC to IL-2, synovial fluid from patients with RA, culture medium of synoviocytes from paitents with RA. 3.Nuclear factor-kappa B antisense oligodeoxynucleotides can inhibit chemotactic function of PBMC from patients with RA.