1,25-Dihydroxyvitamin D3 induces formation of neutrophil extracellular trap-like structures and modulates the transcription of genes whose products are neutrophil extracellular trap-associated proteins: A pilot study

Abstract

&NA; Neutrophils are components of the innate immune system that participate in controlling infectious diseases through microbicidal mechanisms such as phagocytosis, degranulation and the release of neutrophil extracellular traps (NETs). NETs are DNA structures that are released through the decondensation and spreading of chromatin and the adherence of various proteins, including neutrophil elastase (NE), myeloperoxidase (MPO) and peptidyl arginine deiminase 4 (PDA4). Since NETs recovered after treatment of activated polymorphonuclear neutrophils can enhance IL‐1&bgr; and IFN‐&agr; production by LPS‐activated macrophages, they are thought to be keys to the host s defenses and inflammation. 1,25(OH)2D3 has been shown to play an important role in modulating neutrophils activation and in preventing infections. Therefore, the aim of this study was to assess the effect of 1,25(OH)2D3 in modulating induction of the release of NETs and in regulating the transcription of genes whose products in human neutrophils are NETs‐associated proteins, TLRs and interferon. We observed that 1,25(OH)2D3 induced production of NETs‐like structures while also upregulating NE/PAD4/COX‐3/GAPDH mRNA levels. Additionally, we found an increase in TLR7 and type I interferon (IFN) mRNA levels as a result of neutrophil activation by 1,25(OH)2D3. Since the transcription of genes whose products constitute NETs‐associated proteins are differentially‐regulated by 1,25(OH)2D3, we proposed that this might restrict the spread of pathogens, such as virus, by inducing NETs, the expression of TLR7 and secretion of IFN‐&agr;. Our results suggest the potential importance of this hormone in preventing infections by inducing NETs formation.