e-ISSN 2147-8325
Volume : 5 Issue : 3 Year : 2021
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1,25(OH)2 D3, Sistemik Lupus Eritematozus Hastalarında Nötrofil Hücre Dışı Tuzakları ile Endotel Apoptozunu Baskılar [TJI]
TJI. 2017; 5(3): 89-95 | DOI: 10.25002/tji.2017.623

1,25(OH)2 D3, Sistemik Lupus Eritematozus Hastalarında Nötrofil Hücre Dışı Tuzakları ile Endotel Apoptozunu Baskılar

Kusworini Handono1, Benny Arie Pradana2, Radhitio Nugroho2, Dian Hasanah3, Handono Kalim3, Agustina Tri Endharti4, And Fatchiyah4
1Department of Clinical Pathology, Faculty of Medicine Brawijaya University/ Saiful Anwar General Hospital, Malang, Indonesia
2Biomedical Sciences, Master’s Program, Faculty of Medicine Brawijaya University, Malang, Indonesia
3Department of Internal Medicine, Faculty of Medicine Brawijaya University, Saiful Anwar General Hospital, Malang, Indonesia
4Department of Biology, Faculty of Mathematics and Natural Science, Brawijaya University, Malang, Indonesia

Giriş: Sistemik Lupus Eritematozus (SLE), Düşük Yoğunluklu Granülositlerin (DYG) varlığı ile karakterize çok karmaşık bir otoimmün hastalıktır. Bu DYGler, nötrofillerin hücre dışı tuzaklarını (NHT) oluşturma özelliğindedir. D vitamini düzeyleri ise, SLE’li hastalrda normal bireylerdekine göre daha düşük saptanmıştır. Bu çalışmada, Vitamin D [1,25 (OH)2D3] seviyelerinin Vitamin D eksikliği olan SLE hastalarındaki DYG oluşturma endotel hücresi apoptozisi üzerine olan etkisini irdeledik. Gereçler ve Yöntemler: Beş SLE’li ve D vitamini eksiklği olan hastadan elde edilen nötrofiller, 1x10-9 M, 1x10-8 M, ve 10-7M 1,25 (OH)2D3 verilen ve kontrol olarak ta hiç D vitamini uygulanmayan gruplara ayrıldı. Bu gruplardaki nötrofillerin NHT oluşturma özelliği irdelendi. NHT’nin arttırılmaya çalışıldığı bu deneylerden elde edilen hücre üstü sıvılar, insan göbek kordonu veni endotel hücreleri üzerine uygulandı. Histon ve defensin çıkarımı immünofloresan boyama tekniği ile araştırıldı. Endotel hücrelerinin apoptozu, akan hücre ölçeri ile değerlendirildi. Bulgular: Çalışmada, 1x10-8 M 1,25 (OH)2D3 uygulanan nötrofillerin diğer gruplara göre daha az defendin ve histon çıkarımı yaptığı ve daha az endotel hücresi apoptozuna neden olduğu saptandı. Aynı zamanda, histon çıkarımı ile endotel hücresi apoptozu arasında bir bağıntı saptandı. Sonuçlar: D vitamini NHT oluşumunu azaltarak endotel hücresi hasarını azaltır.

Anahtar Kelimeler: Defensin, endotel hücresi, histon, nötrofilin hücre dışı tuzağı, 1,25 (OH)2D3, sistemik lupus eritematozus

1,25(OH)2D3 Inhibits Endothelial Apoptosis by Neutrophil Extracellular Traps Externalization in Systemic Lupus Erythematosus Patients

Kusworini Handono1, Benny Arie Pradana2, Radhitio Nugroho2, Dian Hasanah3, Handono Kalim3, Agustina Tri Endharti4, And Fatchiyah4
1Department of Clinical Pathology, Faculty of Medicine Brawijaya University/ Saiful Anwar General Hospital, Malang, Indonesia
2Biomedical Sciences, Master’s Program, Faculty of Medicine Brawijaya University, Malang, Indonesia
3Department of Internal Medicine, Faculty of Medicine Brawijaya University, Saiful Anwar General Hospital, Malang, Indonesia
4Department of Biology, Faculty of Mathematics and Natural Science, Brawijaya University, Malang, Indonesia

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.

Keywords: Defensin, endothelial, histone, NETs, 1,25 (OH)2D3, Neutrophil extracellular trap

Kusworini Handono, Benny Arie Pradana, Radhitio Nugroho, Dian Hasanah, Handono Kalim, Agustina Tri Endharti, And Fatchiyah. 1,25(OH)2D3 Inhibits Endothelial Apoptosis by Neutrophil Extracellular Traps Externalization in Systemic Lupus Erythematosus Patients. TJI. 2017; 5(3): 89-95
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