Teimourian Shahram, Moghanloo Ehsan
Department of Medical Genetics, Iran University of Medical Sciences, Tehran, Iran; Department of Human Genetics, Tehran University of Medical Sciences, Tehran, Iran; Pediatrics Infectious Diseases Research Center, Department of Infectious Diseases, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Department of Human Genetics, Tehran University of Medical Sciences, Tehran, Iran; Pediatrics Infectious Diseases Research Center, Department of Infectious Diseases, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Department of Microbiology and Immunology, Faculty of Medicine, Kashan University of Medical Sciences, Kashan, Iran.
Mol Immunol. 2015 Aug;66(2):319-24. doi: 10.1016/j.molimm.2015.03.251. Epub 2015 Apr 26.
NETosis has been associated with a particular mode of cell death although it is still controversial as to what extent autophagy is involved in NETosis. Class I/AKT/mTOR pathway is a key regulator of autophagy. PTEN tumor suppressor gene encodes a dual specificity phosphatase that antagonizes the phosphatidylinositol 3-kinase in class the I/AKT/mTOR pathway. In this study, we investigated the effects of PTEN down-regulation as well as overexpression on NETosis. Our results show that 35% of HL-60 differentiated neutrophil-like cells generated NETs by PMA. The portion of the population that produced NETs in PTEN knockdown HL-60 differentiated neutrophils was 9% and in PTEN overexpressed HL-60 differentiated neutrophils, it was 56%. Our results show that increasing PTEN expression increases NETs formation in neutrophils, and its suppression reduces NETs.
尽管自噬在多大程度上参与中性粒细胞胞外诱捕网形成(NETosis)仍存在争议,但NETosis已与一种特定的细胞死亡模式相关联。I类/蛋白激酶B(AKT)/哺乳动物雷帕霉素靶蛋白(mTOR)信号通路是自噬的关键调节因子。磷酸酶及张力蛋白同源物(PTEN)肿瘤抑制基因编码一种双特异性磷酸酶,可在I类/AKT/mTOR信号通路中拮抗磷脂酰肌醇3激酶。在本研究中,我们研究了PTEN下调和过表达对NETosis的影响。我们的结果显示,35%的经佛波酯(PMA)诱导分化的HL-60中性粒细胞样细胞产生了中性粒细胞胞外诱捕网。在PTEN基因敲低的HL-60分化中性粒细胞中,产生中性粒细胞胞外诱捕网的细胞比例为9%,而在PTEN过表达的HL-60分化中性粒细胞中,这一比例为56%。我们的结果表明,增加PTEN表达可增加中性粒细胞中中性粒细胞胞外诱捕网的形成,而抑制PTEN则会减少中性粒细胞胞外诱捕网的形成。