IL-33-induced neutrophil extracellular traps degrade fibronectin in a murine model of bronchopulmonary dysplasia

Jin, Rui; Xu, Junjie; Gao, Qianqian; Mao, Xiaonan; Yin, Jiao; Lu, Keyu; Guo, Yan; Zhang, Mingshun; Cheng, Rui

doi:10.1038/s41420-020-0267-2

Cited by 29 publications

(24 citation statements)

References 47 publications

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“…Lipopolysaccharide stimulation can trigger lung epithelial cells to release alarmin IL‐33, which plays an important role in asthma 30 . In our study, however, lung IL‐33 levels were comparable between the HDM/LPS and HDM‐alone groups (Figure 3e).…”

Section: Resultsmentioning

confidence: 50%

IL‐33/ST2 axis deficiency exacerbates neutrophil‐dominant allergic airway inflammation

Qian

Jiang

et al. 2021

Clin & Trans Imm

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Objective The IL‐33/ST2 axis has been extensively investigated in type 2 eosinophilic inflammation. Here, we aimed to investigate the role of the IL‐33/ST2 axis in neutrophil‐dominant allergic airway inflammation. Methods House‐dust mite (HDM) extract and lipopolysaccharide (LPS) were administered to establish a murine model of neutrophil‐dominant allergic airway inflammation. The formation of neutrophilic extracellular traps (NETs) in the lung tissues was demonstrated by immunofluorescence imaging. Mature IL‐33 in bronchoalveolar lavage fluid (BALF) was detected by Western blotting. The neutrophilic chemokine KC produced by bone marrow‐derived macrophages (BMDMs) or primary alveolar epithelial cells was measured with a commercial ELISA kit. Results In the present study, we observed neutrophilic inflammation and tight junction damage in the lungs of mice sensitised with HDM and LPS. Furthermore, sensitisation with HDM and LPS resulted in the formation of NETs, accompanied by increased levels of mature IL‐33 in the BALF. Moreover, LPS damaged the epithelial tight junction protein occludin directly or indirectly by inducing NET formation. Surprisingly, IL‐33 deficiency augmented neutrophilia and epithelial barrier injury in the lungs of mice after sensitisation with HDM and LPS. Similarly, the absence of ST2 exacerbated the neutrophilic inflammatory response, decreased the expression of occludin and exacerbated the severity of neutrophil‐dominant allergic airway inflammation in an HDM/LPS‐induced mouse model. Mechanistically, BMDMs and alveolar epithelial cells from IL‐33‐ or ST2‐deficient mice tended to produce higher levels of the neutrophilic chemokine KC. Conclusions These results demonstrated that the IL‐33/ST2 axis may play a protective role in neutrophil‐dominant allergic airway inflammation.

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Section: Resultsmentioning

confidence: 50%

IL‐33/ST2 axis deficiency exacerbates neutrophil‐dominant allergic airway inflammation

Qian

Jiang

et al. 2021

Clin & Trans Imm

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“… 17 ). In contrast, NETs cleaved extracellular matrix and degraded fibronectin in the developing lung and epithelial cells 18 . The double-edged roles of NETs in post-epidural fibrosis have not been well documented.…”

Section: Introductionmentioning

confidence: 91%

Neutrophil extracellular traps promote scar formation in post-epidural fibrosis

et al. 2020

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Low back pain following spine surgery is a major complication due to excessive epidural fibrosis, which compresses the lumbar nerve. The mechanisms of epidural fibrosis remain largely elusive. In the drainage samples from patients after spine operation, neutrophil extracellular traps (NETs) and NETs inducer high-mobility group box 1 were significantly increased. In a mouse model of laminectomy, NETs developed in the wound area post epidural operation, accompanied with macrophage infiltration. In vitro, macrophages ingested NETs and thereby increased the elastase from NETs via the receptor for advanced glycation end product. Moreover, NETs boosted the expression of fibronectin in macrophages, which was dependent on elastase and could be partially blocked by DNase. NF-κB p65 and Smad pathways contributed to the increased expression fibronectin in NETs-treated macrophages. In the mouse spine operation model, post-epidural fibrosis was significantly mitigated with the administration of DNase I, which degraded DNA and cleaved NETs. Our study shed light on the roles and mechanisms of NETs in the scar formation post spine operation.

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“…Therefore, these studies suggest that IL‐33 and ILC2 contribute to lung inflammation, airway hyperactivity and long‐term respiratory complications that often affect preterm infants diagnosed with BPD. At the same time, systemic and epithelial cell‐specific overexpression of IL‐33 has been associated with retarded lung development in hyperoxia‐induced BPD in mice 129–131 . These findings suggest that IL‐33 is under tight regulation in the lung, and an imbalance in this pathway can result in alveolar damage.…”

Section: Immune Mediators Are Important In Bpd and Rop Pathogenesismentioning

confidence: 90%

“…At the same time, systemic and epithelial cell‐specific overexpression of IL‐33 has been associated with retarded lung development in hyperoxia‐induced BPD in mice. 129 , 130 , 131 These findings suggest that IL‐33 is under tight regulation in the lung, and an imbalance in this pathway can result in alveolar damage. This is further evident in a study of BPD showing the capacity of IL‐33 to induce neutrophil‐associated extracellular traps that promote degradation of the extracellular matrix.…”

Section: Immune Mediators Are Important In Bpd and Rop Pathogenesismentioning

confidence: 96%

“…This is further evident in a study of BPD showing the capacity of IL‐33 to induce neutrophil‐associated extracellular traps that promote degradation of the extracellular matrix. 131 It has also been speculated that IL‐33 may indirectly enhance TGF‐β expression in the developing lung via IL‐1β activation, thereby promoting neutrophil infiltration. 129 …”

Section: Immune Mediators Are Important In Bpd and Rop Pathogenesismentioning

confidence: 99%

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The immunological link between neonatal lung and eye disease

et al. 2021

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Bronchopulmonary dysplasia (BPD) and retinopathy of prematurity (ROP) are two neonatal diseases of major clinical importance, arising in large part as a consequence of supplemental oxygen therapy used to promote the survival of preterm infants. The presence of coincident inflammation in the lungs and eyes of neonates receiving oxygen therapy indicates that a dysregulated immune response serves as a potential common pathogenic factor for both diseases. This review examines the current state of knowledge of immunological dysregulation in BPD and ROP, identifying similarities in the cellular subsets and inflammatory cytokines that are found in the alveoli and retina during the active phase of these diseases, indicating possible mechanistic overlap. In addition, we highlight gaps in the understanding of whether these responses emerge independently in the lung and retina as a consequence of oxygen exposure or arise because of inflammatory spill‐over from the lung. As BPD and ROP are anatomically distinct, they are often considered discreet disease entities and are therefore treated separately. We propose that an improved understanding of the relationship between BPD and ROP is key to the identification of novel therapeutic targets to treat or prevent both conditions simultaneously.

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IL-33-induced neutrophil extracellular traps degrade fibronectin in a murine model of bronchopulmonary dysplasia

Cited by 29 publications

References 47 publications

IL‐33/ST2 axis deficiency exacerbates neutrophil‐dominant allergic airway inflammation

IL‐33/ST2 axis deficiency exacerbates neutrophil‐dominant allergic airway inflammation

Neutrophil extracellular traps promote scar formation in post-epidural fibrosis

The immunological link between neonatal lung and eye disease

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