Oxidative Stress Contributes to Inflammatory and Cellular Damage in Systemic Lupus Erythematosus: Cellular Markers and Molecular Mechanism

Abstract

Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease with complex pathogenesis, the treatment of which relies exclusively on the use of immunosuppressants. Increased oxidative stress is involved in causing inflammatory and cellular defects in the pathogenesis of SLE. Various inflammatory and cellular markers including oxidative modifications of proteins, lipids, and DNA contribute to immune system dysregulation and trigger an aggressive autoimmune attack through molecular mechanisms like enhanced NETosis, mTOR pathway activation, and imbalanced T-cell differentiation. Accordingly, the detection of inflammatory and cellular markers is important for providing an accurate assessment of the extent of oxidative stress. Oxidative stress also reduces DNA methylation, thus allowing the increased expression of affected genes. As a result, pharmacological approaches targeting oxidative stress yield promising results in treating patients with SLE. The purpose of this review is to examine the involvement of oxidative stress in the pathogenesis and management of SLE.

Identification of the susceptible genes of systemic lupus erythematosus and sepsis: based on immune and oxidative stress-related genes

“…The comparison of expression differences between groups were later performed based on the expression of immune and oxidative stress-related genes, respectively. With the progression of SLE, immune and oxidative stress gradually show high levels of activity, which is consistent with the current ndings [8,12] . The main mechanism of SEP is infection-induced immunosuppression [49] , and oxidative stress makes enhances endothelial dysfunction promoting disease progression [50] .…”

“…Oxidative stress has also been linked to the pathogenesis of SLE by suppressing FOXP3 expression, Treg cell differentiation, and lipid peroxidation metabolites [11,12] . Further r studies have revealed that the tolllike receptor pathway, the HIF-1 pathway, and the mTOR pathway play essential roles in immunological and metabolic regulation during the host response to infection [13,14] .…”

Relationship between bilirubin and systemic lupus erythematosus: A systematic review and meta‐analysis

“…Various markers induce oxidative modifications of proteins, lipids, and DNA, leading to immune system dysfunction and a fierce autoimmune assault. Some of the indicators are improved NETosis, stimulation of the mTOR pathway, and disrupted T‐cell differentiation caused by molecular mechanisms 18,19 …”

“…Some of the indicators are improved NETosis, stimulation of the mTOR pathway, and disrupted T-cell differentiation caused by molecular mechanisms. 18,19 According to certain scientists, bilirubin is a powerful antioxidant that can potentially offer cellular defense against detrimental stimuli. 20 Several studies have indicated a strong correlation between serum bilirubin levels and SLE.…”

Title The Role of the Oxidative State and Innate Immunity Mediated by TLR7 and TLR9 in Lupus Nephritis

“…Arterial hypertension is associated with OS, and its presence in SLE implies a dysregulated ratio of Th1/Th2 cytokines, increased production of IL-17, and insulin resistance. By augmenting the susceptibility of the tiny renal inlet arteries to angiotensin II and the expression of sodium chloride co-transporters, OS may enhance the reabsorption of water and sodium in the renal tubules, precipitating the development of hypertension [77,78]. Nuclear factor E2-related factor 2 (Nrf2) is a vital regulator of the antioxidant response in LN.…”