TY - JOUR
T1 - Oxidative stress-induced aberrant lipid metabolism is an important causal factor for dysfunction of immunocytes from patients with systemic lupus erythematosus
AU - Hu, Changfeng
AU - Zhang, Jida
AU - Hong, Suzhen
AU - Li, Haichang
AU - Lu, Lu
AU - Xie, Guanqun
AU - Luo, Wenqing
AU - Du, Yu
AU - Xie, Zhijun
AU - Han, Xianlin
AU - Wen, Chengping
N1 - Funding Information:
We thank all of the volunteers for their invaluable willingness to donate blood. The work was partially supported by National Natural Science Foundation of China (No. 81803861 and 81774255 ), Natural Science Foundation of Zhejiang Province of China (No. LY20B050006 ), and National Key R&D Program of China ( 2018YFC1705501 ).
Funding Information:
We thank all of the volunteers for their invaluable willingness to donate blood. The work was partially supported by National Natural Science Foundation of China (No. 81803861 and 81774255), Natural Science Foundation of Zhejiang Province of China (No. LY20B050006), and National Key R&D Program of China (2018YFC1705501).
Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2021/2/1
Y1 - 2021/2/1
N2 - 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-α) and autoantibodies (e.g., IgG antiphospholipid 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.
AB - 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-α) and autoantibodies (e.g., IgG antiphospholipid 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.
KW - Autoimmune reaction
KW - Lipidomics
KW - Oxidative stress
KW - Peripheral blood mononuclear cells
KW - Systemic lupus erythematosus
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U2 - 10.1016/j.freeradbiomed.2020.12.006
DO - 10.1016/j.freeradbiomed.2020.12.006
M3 - Article
C2 - 33352222
AN - SCOPUS:85098202664
VL - 163
SP - 210
EP - 219
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
SN - 0891-5849
ER -