Inhibitory effect of iguratimod on Epstein-Barr virus production in Burkitt lymphoma cell line (AKATA) and B lymphoblastoid cells produced by in vitro transformation of Epstein-Barr virus.

Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) has been implicated in Epstein-Barr virus (EBV) reactivation. In this study, we aimed to investigate the role of iguratimod, an NF-κB activator inhibitor, in EBV lytic cycle activation in EBV-infected cells. EBV-producing cells, AKATA, and B-lymphoblastoid cells (BLBC) with 1 μM iguratimod. EBV DNA copy numbers were measured using real-time polymerase chain reaction. The inhibitory effect of iguratimod on NF-κB nuclear translocation in AKATA cells was examined. Immunohistochemical staining revealed significantly increased EBV early antigen diffuse type (EA-D) production in IgG-stimulated AKATA cells and IgM-stimulated BLBC compared with unstimulated cells, whereas co-culture with iguratimod suppressed the production of EBV EA-D. Additionally, AKATA cells/BLBC stimulated with anti-human IgG/IgM showed a significant increase in EBV DNA copy number compared to unstimulated cells, which was significantly reduced by co-culture with iguratimod. Nuclear expression of NF-κB was observed in AKATA cells stimulated with anti-human IgG, and NF-κB expression was suppressed by treatment with iguratimod. These findings suggest that iguratimod may reduce rheumatoid arthritis disease activity by partially inhibiting EBV reactivation. This may partially suppress the onset of RA.