[Neutrophil extracellular traps-induced endothelial cell damage in the pathogenesis of dermatomyositis-associated interstitial lung disease].

Objective

To explore the role of neutrophil extracellular traps (NETs)-induced endothelial cell damage in the pathogenesis of dermatomyositis (DM)-associated interstitial lung disease(ILD).

Methods

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).

Results

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, P<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, P<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, P<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, P<0.005]. Free DNA and KL-6 were positively correlated (r=0.251, P<0.05). The survival of endothelial cells in DM group (53±11)% was lower than that of HC group [(70±5)%, P<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)%, P<0.01].

Conclusion

NETs could play an important role in the pathogenesis of dermatomyositis associated interstitial lung disease, suggesting that NETs may be the potential therapeutic target.