Role of Nrf2 in rheumatoid arthritis.

Background: Rheumatoid arthritis comprises the roots of 19th century and is an autoimmune and chronic inflammatory disorder leading to progressive joint destruction. This erosive joint damage is linked with infiltration of leukocytes along with inflammatory destruction and blood cell formation within the synovial membrane, deprivation of cartilage and bone that leads to incapacitative pain. The changes in synovium include its proliferation that leads to pannus formation and this ultimately leads to the invasion and erosions causing the destruction of joints. It is also defined as the destructive or chronic disease with a longer time duration that takes articular consideration as a feature.

Objective: The factors that can lead to RA includes inflammatory cascades, increased levels of (TNF-α) tumor necrosis factor α, IL-1b and IL-17 (interleukins) along with reduced levels of Nrf2 factors (nuclear factor-erythroid 2-related factor-2). Nrf2 binds effectively to antioxidant response elements (ARE) that mainly encodes majority of the phase II antioxidant enzymes as well as stress receptive proteins including glutathione S-transferase (GSH), heme oxygenase-1 (HO-1), peroxiredoxin I, all these act by cellular defense mechanism and removes the cytotoxic electrophiles along with the ROS that is reactive oxygen species. Nrf2 also responds to the inflammatory stimulus and protect the tissues from the inflammatory tissues.