Netting Gut Disease: Neutrophil Extracellular Trap in Intestinal Pathology

Chen, Kai; Shao, Liang; Wang, Feng; Shen, Xiaofei; Xia, Xuefeng; Kang, Xing; Song, Peng; Wang, Meng; Lu, Xiaofeng; Wang, Chao; Hu, Qiongyuan; Liu, Song; Guan, Wenxian

doi:10.1155/2021/5541222

Cited by 17 publications

(16 citation statements)

References 101 publications

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“…These experiments documented that QJHTD inhibited the formation of PMA-stimulated NETs. There are two main pathways for the formation of NETs: pyrolysis NET formation dependent on NADPH oxidase and non-pyrolysis NET formation independent of NADPH oxidase (Chen et al, 2021). PMA activates protein kinase C, which in turn stimulates the production of ROS by activating NADPH oxidase (Fuchs et al, 2007;De Bont et al, 2018;Fousert et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Network Pharmacology and Experimental Validation to Explore the Mechanism of Qing-Jin-Hua-Tan-Decoction Against Acute Lung Injury

et al. 2022

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Qing-Jin-Hua-Tan-Decoction (QJHTD), a classic famous Chinese ancient prescription, has been used for treatment of pulmonary diseases since Ming Dynasty. A total of 22 prototype compounds of QJHTD absorbed into rat blood were chosen as candidates for the pharmacological network analysis and molecular docking. The targets from the intersection of compound target and ALI disease targets were used for GO and KEGG enrichment analyses. Molecular docking was adopted to further verify the interactions between 22 components and the top 20 targets with higher degree values in the component–target–pathway network. In vitro experiments were performed to verify the results of network pharmacology using SPR experiments, Western blot experiments, and the PMA-induced neutrophils to produce neutrophil extracellular trap (NET) model. The compound–target–pathway network includes 176 targets and 20 signaling pathways in which the degree of MAPK14, CDK2, EGFR, F2, SRC, and AKT1 is higher than that of other targets and which may be potential disease targets. The biological processes in QJHTD for ALI mainly included protein phosphorylation, response to wounding, response to bacterium, regulation of inflammatory response, and so on. KEGG enrichment analyses revealed multiple signaling pathways, including lipid and atherosclerosis, HIF-1 signaling pathway, renin–angiotensin system, and neutrophil extracellular trap formation. The molecular docking results showed that baicalin, oroxylin A-7-glucuronide, hispidulin-7-O-β-D-glucuronide, wogonoside, baicalein, wogonin, tianshic acid, and mangiferin can be combined with most of the targets, which might be the core components of QJHTD in treatment of ALI. Direct binding ability of baicalein, wogonin, and baicalin to thrombin protein was all micromolar, and their KD values were 11.92 μM, 1.303 μM, and 1.146 μM, respectively, revealed by SPR experiments, and QJHTD could inhibit Src phosphorylation in LPS-activated neutrophils by Western blot experiments. The experimental results of PMA-induced neutrophils to produce NETs indicated that QJHTD could inhibit the production of NETs. This study revealed the active compounds, effective targets, and potential pharmacological mechanisms of QJHTD acting on ALI.

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Section: Discussionmentioning

confidence: 99%

Network Pharmacology and Experimental Validation to Explore the Mechanism of Qing-Jin-Hua-Tan-Decoction Against Acute Lung Injury

et al. 2022

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“…Previous studies have mostly focused on the harmful effects of NETs and the development of diseases. A review of the role of NETs in the intestine by Chen et al was published in 2021 (134). They mainly concentrate on the harmful effects of NETs on intestinal diseases, slighting the protective role of NETs in inflammation, such as promoting immune thrombosis to reduce colonic bleeding.…”

Section: Discussionmentioning

confidence: 99%

PADs and NETs in digestive system: From physiology to pathology

et al. 2023

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Peptidylarginine deiminases (PADs) are the only enzyme class known to deiminate arginine residues into citrulline in proteins, a process known as citrullination. This is an important post-translational modification that functions in several physiological and pathological processes. Neutrophil extracellular traps (NETs) are generated by NETosis, a novel cell death in neutrophils and a double-edged sword in inflammation. Excessive activation of PADs and NETs is critically implicated in their transformation from a physiological to a pathological state. Herein, we review the physiological and pathological functions of PADs and NETs, in particular, the involvement of PAD2 and PAD4 in the digestive system, from inflammatory to oncological diseases, along with related therapeutic prospects.

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“…Intestinal IRI is a clinical problem that occurs most commonly after acute mesenteric ischemia, traumatic/hemorrhagic or septic shock, burns, and surgery. It can lead to multiple organ dysfunction and mortality in critically ill patients ( 147 – 149 ). Neutrophils may contribute to intestinal IRI by forming ETs ( 108 , 112 ).…”

Section: Extracellular Traps In Organ Ischemia Reperfusion Injurymentioning

confidence: 99%

The role of extracellular traps in ischemia reperfusion injury

Zhang

et al. 2022

Front. Immunol.

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In response to strong signals, several types of immune cells release extracellular traps (ETs), which are web-like structures consisting of DNA decorated with various protein substances. This process is most commonly observed in neutrophils. Over the past two decades, ET formation has been recognized as a unique mechanism of host defense and pathogen destruction. However, the role of ETs in sterile inflammation has only been studied extensively in recent years. Ischemia reperfusion injury (IRI) is a type of sterile inflammatory injury. Several studies have reported that ETs have an important role in IRI in various organs. In this review, we describe the release of ETs by various types of immune cells and focus on the mechanism underlying the formation of neutrophil ETs (NETs). In addition, we summarize the role of ETs in IRI in different organs and their effects on tumors. Finally, we discuss the value of ETs as a potential therapeutic target for organ IRI and present possible challenges in conducting studies on IRI-related ETs as well as future research directions and prospects.

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Netting Gut Disease: Neutrophil Extracellular Trap in Intestinal Pathology

Cited by 17 publications

References 101 publications

Network Pharmacology and Experimental Validation to Explore the Mechanism of Qing-Jin-Hua-Tan-Decoction Against Acute Lung Injury

Network Pharmacology and Experimental Validation to Explore the Mechanism of Qing-Jin-Hua-Tan-Decoction Against Acute Lung Injury

PADs and NETs in digestive system: From physiology to pathology

The role of extracellular traps in ischemia reperfusion injury

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