CD40/TNF receptor associated factor 1 expression and NF-κB-dependent proinflammatory gene expression in rheumatoid arthritis

Abstract

Objective: To investigatea cellular/molecular mechanism of the CD40/TRAF1 signalling pathway involved in Rheumatoid arthritis (RA). Methods: 16 patients with active RA and 9 patients with Fractures who underwent total knee or hip replacement in The First Affiliated Hospital of Soochow University were included in the study. Synovial tissues (ST) and serum were obtained from each patient. The CD40, TRAF1, NF-κB p65 were detected by ELISA and Immunohistochemistry in serum and tissue respectively. Real time-PCR (RT-PCR) was applied to measure NF-κB-related gene expression. Results: CD40 and TRAF1 positive area (%) in RA patients were 28.7±5.4, 34.3±4.8 respectively, which were significantly higher (P<0.05) than Fracture controls (21.2±9.5, 21.6±8.7 respectively). The expression of total NF-κB p65, and phospho-NF-κB p65 proteins, as well as NF-κB-related gene expression, including cytokines (TNFα, IL-6), chemokines (MCP-1),and adhesion molecules (ICAM-1) were significantly higher in the ST of RA patients compared to Fracture controls. Conclusion: It is thus possible that the CD40/TRAF1 pathway acted as a positive regulator through NF-κB activation and NF-κB-dependent proinflammatory genes in RA.