Reduction of Oxidative Stress in Peripheral Blood Mononuclear Cells Attenuates the Inflammatory Response of Fibroblast-like Synoviocytes in Rheumatoid Arthritis

Int J Mol Sci. 2021 Nov 17;22(22):12411. doi: 10.3390/ijms222212411.

Abstract

The production and oxidation mechanism of reactive oxygen species (ROS) are out of balance 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 synovial 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 synoviocytes (FLSs) from patients with RA were stimulated with PBMCs and the expression of inflammation-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 severity, 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 suppress inflammatory response of FLSs through ROS regulation in PBMCs.

Keywords: cytokines; helper T cells; reactive oxygen species; regulatory T cells; rheumatoid arthritis.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Arthritis, Rheumatoid / blood*
  • Arthritis, Rheumatoid / immunology*
  • Arthritis, Rheumatoid / pathology
  • Case-Control Studies
  • Cells, Cultured
  • Coculture Techniques
  • Cytokines / metabolism
  • Female
  • Fibroblasts / immunology*
  • Humans
  • Inflammation / metabolism
  • Male
  • Middle Aged
  • Mitochondria / metabolism
  • Oxidative Stress*
  • Reactive Oxygen Species / metabolism*
  • Severity of Illness Index
  • Synovial Fluid / metabolism
  • Synoviocytes / immunology*
  • T-Lymphocytes, Helper-Inducer / immunology*
  • T-Lymphocytes, Regulatory / immunology*

Substances

  • Cytokines
  • Reactive Oxygen Species