Journal
FREE RADICAL BIOLOGY AND MEDICINE
Volume 163, Issue -, Pages 210-219Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2020.12.006
Keywords
Systemic lupus erythematosus; Peripheral blood mononuclear cells; Lipidomics; Oxidative stress; Autoimmune reaction
Funding
- National Natural Science Foundation of China [81803861, 81774255]
- Natural Science Foundation of Zhejiang Province of China [LY20B050006]
- National Key R&D Program of China [2018YFC1705501]
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The close relationships among oxidative stress, dyslipidaemia, inflammation, and autoimmune response in SLE patients contribute to dysfunction and dysregulation of immunocytes. Aberrant lipid metabolism in immunocytes, induced by oxidative stress, may lead to increased production of IgG autoantibodies and cytokines in the early stages of the disease. Treatment with a natural antioxidant can correct the aberrant lipid metabolism and reduce autoimmune reactions, suggesting a potential drug treatment for SLE with fewer adverse effects.
There exist close relationships among oxidative stress, dyslipidaemia, inflammation, and autoimmune response in patients with systemic lupus erythematosus (SLE). Dysfunction and/or dysregulation of immunocytes is one of the major characteristics of SLE pathogenesis. Lipids play many important roles in biological processes and cellular functions. We hypothesized that oxidative stress-induced aberrant lipid metabolism and integrity presented in immunocytes is one of the early events in patients, thereby leading to enhanced production of IgG autoantibodies and cytokines. Herein, shotgun lipidomics was employed for quantitative analysis of cellular lipidomes in peripheral blood mononuclear cells (PBMC) both freshly isolated from SLE patients and cultured with treatment. The levels of IgG autoantibodies and cytokines in cell culture media and serum samples from lupus-prone mice treated with a natural, powerful antioxidant isotonix OPC-3 were measured by ELISA kits. IgG antibody deposition in glomeruli of the mice was determined by immunofluorescence analysis. Lipidomics analysis of PBMC from 33 SLE patients and 28 healthy controls revealed aberrant lipid metabolism in PBMC from the patients. The changes included significantly reduced plasmalogens, markedly increased lysophospholipids, altered phosphatidylserines, and accumulated 4-hydroxyalkenals. These alterations of lipids in SLE PBMC could be significantly corrected after cultured with the antioxidant in vitro. Parallel to the IgG antibody deposition in glomeruli, the concentrations of cytokines (i.e., IL-10, IL-6, and TNF-alpha) and autoantibodies (e.g., IgG anti-phospholipid and anti-dsDNA antibodies) in culture medium and serum samples from the mice after treatment with the antioxidant were also significantly reduced compared with those of the SLE group. The results clearly demonstrated that correction of the aberrant lipid metabolism led to inhibition of the autoimmune reactions of PBMC after reduction of the increased oxidative stress. The current study also revealed potential drug treatment of SLE with lesser adverse effects through reducing the aberrant lipid metabolism with an effective antioxidant.
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