1,25(OH)₂D3 inhibits endothelial apoptosis by neutrophil extracellular traps externalization in systemic lupus erythematosus patients

Introduction: Systemic Lupus Erythematosus (SLE) is a very complicated autoimmune disease which is characterized by the presence of abnormal neutrophils known as Low Density Granulocytes (LDGs). These LDGs have increased capacity to produce Neutrophil Extracellular Traps (NETs). Vitamin D levels in SLE patients were significantly lower than that of healthy subjects. This study aims to investigate the effects of vitamin D [1,25 (OH)₂D3] on NETosis and endothelial cell apoptosis in SLE patients with vitamin D deficiency. Materials and Methods: Neutrophils of five SLE patients with vitamin D deficiency were treated with four different doses of 1,25 (OH)₂D3:0 M as a control, 1x10^-9 M, 1x10^-8 M, and 10^-7M. Phorbol myristate Acetate (PMA) were given to induce production of NETs. The supernatant obtained from NETs induction was cocultured with Human Umbilical Vein Endodethial Cells (HUVECs). Histone and defensin externalization was investigated by immunofluorescence staining. Endothelial apoptosis was investigated by flow cytometry. Results: This study shows that neutrophils treated with 1x10^-8 M of 1,25 (OH)₂D3 had significantly lower defensin, histone externalization, and endothelial cell apoptosis compared to those caused by other doses. There was also a positive correlation between histone externalization and endothelial apoptosis. Conclusion: Vitamin D inhibits endothelial damage by reducing the NETs development.