Oxidative Stress in Rheumatoid Arthritis: What the Future Might Hold regarding Novel Biomarkers and Add-On Therapies

Figure 3

Cellular and molecular mechanisms of oxidative stress and inflammation in rheumatoid arthritis. Multidirectional interconnections are seen in the cellular and molecular mechanisms involved in the initiation and progression of articular damage in rheumatoid arthritis, so that oxidative stress may imply increased inflammation and vice versa, ultimately leading to a vicious cycle through which the hallmark of rheumatoid arthritis, i.e., synovitis, becomes established. (1) Arrival of inflammatory cells in the synovium; (2) establishment of synovitis; (3) soluble proinflammatory mediators produced by inflammatory cells; (4) direct effector mechanisms (cell activation, transcription of proinflammatory genes); (5) persistent synovitis and irreversible articular damage. ACPA: anticitrullinated protein antibodies; FLS: fibroblast-like synoviocyte; GM-CSF: granulocyte-macrophage colony-stimulating factor; H₂O₂: hydrogen peroxide; IL-1: interleukin 1; IL-6: interleukin 6; NF-κB: nuclear factor-κB; MAPK: mitogen-activated protein kinase; RF: rheumatoid factor; RNS: reactive nitrogen species; ROS: reactive oxygen species; TNF: tumor necrosis factor.