Vitamin D Prevents Endothelial Damage Induced by Increased Neutrophil Extracellular Traps Formation in Patients with Systemic Lupus Erythematosus

ABSTRACT: to investigate the effects of Vitamin D calcitriol/1,25(OH)2D3 on NETosis in systemic lupus erythematosus (SLE) patients with hypovitamin D. Methods: neutrophlis of fve SLE patients with hypovitamin D were divided into 4 groups, P0 (0 nM/control), P1 (1 nM), P2 (10 nM), and P3 (100 nM) as cultured samples. Phorbol Myristate Acetate (PMA) was used to stimulate NETs formation. The supernatant was separated and cocultured with HUVECs. Externalization of Neutrophil Elastase (NE) and Myeloperoxidase (MPO) during NETosis was measured by immunofluorescence and ELISA respectively. Early and late apoptosis of endothelial cell was measured by flowcytometry using cell death kit (Annexin V and PI antibody). Results: this study showed signifcant decrease in early apoptosis with 10 nM of 1,25(OH)2D3 compared to control group. Signifcance of NE externalization found in all treatment groups (p<0.05), while MPO absorbance in the same tendency but not statistically signifcant. Further analysis also found a moderate positive correlation between NE externalizations with early apoptosis. Conclusion: vitamin D 1,25(OH)2D3 could reduce endothelial damage by decreasing NETosis activity. This result may reveal the possibility of Vitamin D as supplementary therapy for SLE patients with hypovitamin D to prevent endothelial damage.
Key words: NETs, NE, MPO, 1,25(OH)2D3, HUVECs
Author: Kusworini Handono, Yona One Sidarta, Benny A. Pradana, Radhitio A. Nugroho, Ivan A. Hartono, Handono Kalim, Agustina T. Endharti
Journal Code: jpkedokterangg140281