Cytokine Production and NET Formation by Monosodium Urate-Activated Human Neutrophils Involves Early and Late Events, and Requires Upstream TAK1 and Syk

Tatsiy, Olga; Mayer, Thomas Z.; Oliveira, Vanessa de Carvalho; Sylvain-Prévost, Stéphanie; Isabel, M.; Dubois, Claire M.; McDonald, Patrick P.

doi:10.3389/fimmu.2019.02996

Cited by 33 publications

(42 citation statements)

References 51 publications

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“…The generation of ROS is required for NETosis by the activation of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase [25]. Indeed, it has recently been shown that MSU crystals induce NETosis in a ROS-dependent manner [26,27]. In the current research, we showed that the formation of NETs and ROS levels were signi cantly increased in patients with AGA.…”

Section: Discussionmentioning

confidence: 51%

MiR-3146 Induces Neutrophil Extracellular Traps to Aggravate Acute Gouty Arthritis

Shan

Yang

Feng

et al. 2021

Preprint

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MiR-3146 plays an important role in the formation of neutrophil extracellular traps (NETs) during the pathogenesis of acute gouty arthritis (AGA).The aim of our study was to explore the underlying role and molecular mechanism of miR-3146 in the formation of neutrophil extracellular traps (NETs) during the pathogenesis of acute gouty arthritis (AGA). The expression of miR-3146 and sirtuin 1 (SIRT1) was determined by real-time PCR and western blot. The luciferase reporter assay was performed to identify the targeting relationship between miR-3146 and SIRT1. Reactive oxygen species (ROS) production was detected by fluorescent staining. NETs formation was demonstrated via immunofluorescence staining and ELISA method. AGA model was induced in rats to verify the effects of miR-3146 inhibition on histopathological changes and NETs. Here, we found miR-3146 expression was dramatically increased in neutrophils of patients with AGA, presenting higher levels of NETs. Monosodium urate (MSU) crystals significantly increased miR-3146 expression and ROS production in neutrophils. The NETs process was also triggered by MSU crystals. Furthermore, we verified the interaction between miR-3146 and SIRT1. Additionally, antagomir-3146-based therapy effectively inhibited the formation of NETs in rats with AGA. MiR-3146-mediated NETs formation may play a potential role in the pathogenesis of AGA.

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Section: Discussionmentioning

confidence: 51%

MiR-3146 Induces Neutrophil Extracellular Traps to Aggravate Acute Gouty Arthritis

Shan

Yang

Feng

et al. 2021

Preprint

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“…We further confirmed that TREM-1 activation potentiated the activation of key pathways implicated in NETosis. Recent reports identified several key steps of NETosis, including calcium flux, 38 the generation of ROS, 39 and the activation of different proteins, such as PLCγ 40 and SYK, 29,31 leading to PAD4 and Cit-H3 activation. Our data show that TREM-1 activation potentiates all of these steps in vitro and in vivo, further reinforcing its key role during NETosis.…”

Section: Discussionmentioning

confidence: 99%

“…25 These findings have been further confirmed in several studies, 26,27 and some of these intracellular pathways have been further shown to play important roles in NETosis. [28][29][30] We recently showed that the pharmacological inhibition of TREM-1 (with the synthetic peptide LR12) or the genetic ablation of TREM-1 in endothelial cells reduced neutrophil infiltration, vascular endothelial dysfunction, and death in various experimental septic shock models. 21 Considering the strong connection between the TREM-1 and TLR4 signaling pathways, the effect of TLR4 activation on NET production, and the deleterious role of NETs in the early phase of sepsis by promoting endothelial activation and dysfunction, we hypothesized that TREM-1 plays a role in NET generation and/or potentiates the deleterious effects of NETs.…”

Section: Introductionmentioning

confidence: 99%

Potentiation of NETs release is novel characteristic of TREM-1 activation and the pharmacological inhibition of TREM-1 could prevent from the deleterious consequences of NETs release in sepsis

Boufenzer¹,

Carrasco²,

Jolly³

et al. 2021

Cell Mol Immunol

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During sepsis, neutrophil activation induces endothelial cell (EC) dysfunction partly through neutrophil extracellular trap (NET) release. The triggering receptor expressed on myeloid cell-1 (TREM-1) is an orphan immune receptor that amplifies the inflammatory response mediated by Toll-like receptor-4 (TLR4) engagement. Although the key role of TLR4 signaling in NETosis is known, the role of TREM-1 in this process has not yet been investigated. Here, we report that TREM-1 potentiates NET release by human and murine neutrophils and is a component of the NET structure. In contrast, pharmacologic inhibition or genetic ablation of TREM-1 decreased NETosis in vitro and during experimental septic shock in vivo. Moreover, isolated NETs were able to activate ECs and impair vascular reactivity, and these deleterious effects were dampened by TREM-1 inhibition. TREM-1 may, therefore, constitute a new therapeutic target to prevent NETosis and associated endothelial dysfunction.

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“…RNAseq-RNA sequencing; NETosis-neutrophil extracellular trap formation. [54,55] The transcriptomes of mature blood neutrophils can be altered by even minor environmental cues, with gene expression changes observed after brief bouts of exercise [48]. A substantial number of these genes were unique to neutrophils, with only 16% overlap to PBMC gene responses to exercise.…”

Section: Homeostatic Transcriptionmentioning

confidence: 99%

Current Understanding of the Neutrophil Transcriptome in Health and Disease

Garratt

2021

Cells

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Neutrophils are key cells of the innate immune system. It is now understood that this leukocyte population is diverse in both the basal composition and functional plasticity. Underlying this plasticity is a post-translational framework for rapidly achieving early activation states, but also a transcriptional capacity that is becoming increasingly recognized by immunologists. Growing interest in the contribution of neutrophils to health and disease has resulted in more efforts to describe their transcriptional activity. Whilst initial efforts focused predominantly on understanding the existing biology, investigations with advanced methods such as single cell RNA sequencing to understand interactions of the entire immune system are revealing higher flexibility in neutrophil transcription than previously thought possible and multiple transition states. It is now apparent that neutrophils utilise many forms of RNA in the regulation of their function. This review collates current knowledge on the nuclei structure and gene expression activity of human neutrophils across homeostasis and disease, before highlighting knowledge gaps that are research priority areas.

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Cytokine Production and NET Formation by Monosodium Urate-Activated Human Neutrophils Involves Early and Late Events, and Requires Upstream TAK1 and Syk

Cited by 33 publications

References 51 publications

MiR-3146 Induces Neutrophil Extracellular Traps to Aggravate Acute Gouty Arthritis

MiR-3146 Induces Neutrophil Extracellular Traps to Aggravate Acute Gouty Arthritis

Potentiation of NETs release is novel characteristic of TREM-1 activation and the pharmacological inhibition of TREM-1 could prevent from the deleterious consequences of NETs release in sepsis

Current Understanding of the Neutrophil Transcriptome in Health and Disease

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