Inhibition of Cytokines and ICAM-1 Induction in Rheumatoid Fibroblasts by anti-NF-κB Reagents

Abstract

The role of the transcription factor, nuclear factor NF-κB, in the induction of cytokines and intercellular adhesion molecule-1 (ICAM-1) on stimulation with interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α) was studied in primary rheumatoid synovial fibroblasts (RSF) obtained from patients with rheumatoid arthritis (RA). The production of GM-CSF, IL-6, and IL-8 and the expression of ICAM1 were augmented after nuclear translocation of NF-κB induced by treatment with IL-1 or TNF-α. We examined the effects of N-acetyl-l-cysteine (NAC) and acetylsalicylic acid (aspirin) on the induction of proinflammatory cytokines and ICAM-1. Pretreatment of RSF with NAC inhibited nuclear translocation of NF-κB completely, and the induction of these cytokines and ICAM-1 was markedly suppressed. On the other hand, the effect of aspirin was only partial. These observations indicate the pivotal role of NF-κB in RA pathogenesis, thus highlighting the possibility of a novel therapeutic strategy.