1,25(OH)2D3 inhibits endothelial apoptosis by neutrophil extracellular traps externalization in systemic lupus erythematosus patients; [1,25(OH)2 D3, sistemik lupus eritematozus hastalarinda nötrofil hücre dişi tuzaklari ile endotel apoptozunu baskilar]

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Kusworini Handono, Benny Arie Pradana, Radhitio Adi Nugroho, Dian Hasanah, Handono Kalim, Agustina Tri Endharti, Fatchiyah

2017 Turkish Journal of Immunology Vol. 5 Issue 3 Article Cited by 2 Quartile

Abstract

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. © 2017 Turkish Journal of Immunology. All rights reserved.

Affiliations

Department of Clinical Patholog, Faculty of Medicine, Saiful Anwar General Hospital, Brawijaya University, Malang, Indonesia; Faculty of Medicine, Brawijaya University, Malang, Indonesia; Department of Internal Medicine, Faculty of Medicine, Saiful Anwar General Hospital, Brawijaya University, Malang, Indonesia; Department of Parasitology, Faculty of Medicine, Brawijaya University, Malang, Indonesia; Department of Biology, Faculty of Mathematics and Natural Science, Brawijaya University, Malang, Indonesia