Zhang Y, Yan B, Liu Y
Department of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu 610041, China.
Zhonghua Nei Ke Za Zhi. 2017 Sep 1;56(9):650-654. doi: 10.3760/cma.j.issn.0578-1426.2017.09.006.
To explore the role of neutrophil extracellular traps (NETs)-induced endothelial cell damage in the pathogenesis of dermatomyositis (DM)-associated interstitial lung disease(ILD). Serum free DNA and krebs von den lungen-6 (KL-6) level were tested in healthy controls, dermatomyositis patients with or without interstitial lung disease (DM-ILD and DM-NILD). Subjects' peripheral blood neutrophils were stimulated with phorbol 12-myristate 13-acetate (PMA), then human umbilical vein endothelial cells (HUVECs) were co-cultured with NETs. The cell morphology was observed by the inverted phase contrast microscope. Cell viability was detected by cell counting kit-8 (CCK8). The concentration of serum free DNA in DM patients [(271.27± 76.53) μg/L] was significantly higher than that in health control (HC)[(152.89±37.34) μg/L, <0.001]. Moreover, free DNA level in DM-ILD patients [(302.67±74.15) μg/L] was higher than that in DM-NILD patients [(235.59±63.55 ) μg/L, <0.005]. The concentration of KL-6in DM patients [(3.08±2.07) μg/L]was higher than that in HC[(0.87±0.51) μg/L, <0.001]. Similarly, KL-6 in DM-ILD patients [(4.00±2.44) μg/L ] was higher than that of DM-NILD patients [(2.03±0.61) μg/L, <0.005]. Free DNA and KL-6 were positively correlated (=0.251, <0.05). The survival of endothelial cells in DM group (53±11)% was lower than that of HC group [(70±5)%, <0.001]. Not surprisingly, the survival of endothelial cells in DM-ILD group (44±4) % was lower than that in DM-NILD group [(61±8)%, <0.01]. NETs could play an important role in the pathogenesis of dermatomyositis associated interstitial lung disease, suggesting that NETs may be the potential therapeutic target.
探讨中性粒细胞胞外陷阱(NETs)诱导的内皮细胞损伤在皮肌炎(DM)相关间质性肺病(ILD)发病机制中的作用。检测健康对照者、有或无间质性肺病的皮肌炎患者(DM-ILD和DM-NILD)的血清游离DNA和克雷布斯冯登卢根-6(KL-6)水平。用佛波酯12-肉豆蔻酸酯13-乙酸酯(PMA)刺激受试者外周血中性粒细胞,然后将人脐静脉内皮细胞(HUVECs)与NETs共培养。通过倒置相差显微镜观察细胞形态。用细胞计数试剂盒-8(CCK8)检测细胞活力。DM患者血清游离DNA浓度[(271.27±76.53)μg/L]显著高于健康对照(HC)组[(152.89±37.34)μg/L,P<0.001]。此外,DM-ILD患者的游离DNA水平[(302.67±74.15)μg/L]高于DM-NILD患者[(235.59±63.55)μg/L,P<0.005]。DM患者的KL-6浓度[(3.08±2.07)μg/L]高于HC组[(0.87±0.51)μg/L,P<0.001]。同样,DM-ILD患者的KL-6[(4.00±2.44)μg/L]高于DM-NILD患者[(2.03±0.61)μg/L,P<0.005]。游离DNA与KL-6呈正相关(r=0.251,P<0.05)。DM组内皮细胞存活率(53±11)%低于HC组[(70±5)%,P<0.001]。不出所料,DM-ILD组内皮细胞存活率(44±4)%低于DM-NILD组[(61±8)%,P<0.01]。NETs可能在皮肌炎相关间质性肺病的发病机制中起重要作用,提示NETs可能是潜在的治疗靶点。