Reduction of oxidative stress in peripheral blood mononuclear cells attenuates the inflammatory response of fibroblast‐like synoviocytes in rheumatoid arthritis

Abstract

The production and oxidation mechanism of reactive oxygen species (ROS) are out of bal-ance in rheumatoid arthritis (RA). However, the correlation between ROS and T cell subsets in RA remains unclear. Peripheral blood mononuclear cells (PBMCs) from patients with RA (n = 40) and healthy controls (n = 10) were isolated from whole blood samples. Synovial tissues (n = 3) and syn-ovial fluid (n = 10) were obtained from patients with RA. The repartition of T cell subsets and expression of ROS and cytokines were examined according to RA severity. Fibroblast‐like synovio-cytes (FLSs) from patients with RA were stimulated with PBMCs and the expression of inflamma-tion‐related molecules were measured by RT‐PCR and cytokine array. Regulatory T cells from patients with moderate (5.1 > DAS28 ≥ 3.2) RA showed the highest expression of mitochondrial ROS among the groups based on disease severity. Although ROS levels steadily increased with RA se-verity, there was a slight decline in severe RA (DAS28 ≥ 5.1) compared with moderate RA. The expression of inflammatory cytokines in RA FLSs were significantly inhibited when FLSs were co-cultured with PBMCs treated with ROS inhibitor. These findings provide a novel approach to sup-press inflammatory response of FLSs through ROS regulation in PBMCs.