Netrin-1 prevents the attachment of monocytes to endothelial cells via an anti-inflammatory effect

Lin, Zhaoheng; Jin, Jing; Bai, Weirong; Li, Jiao; Shan, Xiyun

doi:10.1016/j.molimm.2018.08.021

Cited by 32 publications

(37 citation statements)

References 25 publications

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“…Here, we found that netrin-1 treatment reduced UV-Binduced ROS overproduction and NOX-4 expression, suggesting a novel antioxidant capacity of netrin-1. Consistently, it has been recently shown that netrin-1 displays an UNC5b- dependent anti-inflammatory effect in endothelial cells through suppressing TNF-a-induced production of the cytokines MCP-1, IL-1b and IL-6 as well as expression of the vascular adhesion molecules VCAM-1, ICAM-1 and E-selectin [23]. Exacerbation of cell death and mitochondrial dysfunction has been linked to decline in ESC function in response to UV-B radiation.…”

Section: Discussionsupporting

confidence: 61%

Netrin-1 plays a critical role in regulating capacities of epidermal stem cells upon ultraviolet-B (UV-B) irradiation

Cao

Zhao

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

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Loss of the capacities of epidermal stem cells (ESCs) induced by ultraviolet-B (UV-B) irradiation has been widely associated with various skin diseases. Netrin-1, a member of the axonal guidance protein family, has displayed diverse biological functions in different types of cells and tissues, mediated by its specific receptor UNC-5 homolog B (UNC5b). In this study, we examined the physiological functions of netrin-1 and UNC5b in ESCs upon UV-B exposure. Our results indicate that UNC5b is expressed in ESCs, and its expression is upregulated in response to UV-B radiation. We found that treatment with netrin-1 prevented UV-B radiation-induced oxidative stress by reducing the generation of reactive oxygen species (ROS) and expression of NADPH oxidase 4 (NOX-4). Additionally, treatment with netrin-1 improved UV-B radiation-induced mitochondrial dysfunction by increasing mitochondrial membrane potential (MMP) levels and adenosine triphosphate (ATP) production. The presence of netrin-1 attenuated UV-B radiation-induced lactic dehydrogenase (LDH) release. UV-B exposure resulted in the loss of the capacities of ESCs by reducing the expressions of integrin b1 and Krt19, the two major ESC markers. Importantly, this process was prevented by netrin-1. Silencing of UNC5b abolished the effects of netrin-1 on the expression of integrin b1 and Krt19, suggesting that the effects of netrin-1 in maintaining the capacities of ESCs are dependent on UNC5b. Mechanistically, we found that the Wnt/b-catenin signalling may be involved. Our findings suggest that netrin-1 may serve as a therapeutic agent for the treatment of skin diseases. ARTICLE HISTORY

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Section: Discussionsupporting

confidence: 61%

Netrin-1 plays a critical role in regulating capacities of epidermal stem cells upon ultraviolet-B (UV-B) irradiation

Cao

Zhao

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

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“…Studies in human and animal models have revealed that Netrin‐1 can modulate monocyte/macrophage migration and takes part in limiting the transmigration of these cells into the tissues in inflammatory conditions via its receptor Unc5b thus controlling the inflammation. This interaction is important to hamper excessive inflammatory reactions.…”

Section: Discussionmentioning

confidence: 99%

“…In an in vivo acute pulmonary inflammation model, the expression of Netrin‐1 by vascular endothelium was down‐regulated during inflammation concurrent with the migration of neutrophils to the tissue . In a study conducted by Lin, et al revealed that Netrin‐1 blocked the attachment of monocytes to endothelial cells via suppression of TNF‐α‐induced vascular adhesion molecules and suppression of TNF‐α‐induced NF‐κB activation and production of MCP‐1, IL‐1β, and IL‐6. In another study, the role of Netrin‐1 and its receptor was investigated in atherosclerosis and it has been shown that Netrin‐1 was secreted in human and mouse atheroma and inhibited CCL2‐ and CCL19‐directed macrophage migration acting via its receptor UNC5b .…”

Section: Discussionmentioning

confidence: 99%

“…This molecule suppressed TNF‐α‐induced vascular adhesion molecules and hampered the adhesion of monocytes to endothelial cells. Moreover, Netrin‐1 prevented NF‐κB activation and revealed an anti‐inflammatory function . It has been reported that Netrin‐1 regulates the inflammatory response through suppression of COX‐2–mediated PGE2 production and HIF‐1alpha‐dependent induction of Netrin‐1 has been demonstrated to attenuate hypoxia‐elicited inflammation at mucosal surfaces .…”

Section: Introductionmentioning

confidence: 96%

“…Moreover, Netrin-1 prevented NF-κB activation and revealed an anti-inflammatory function. 10 It has been reported that Netrin-1 regulates the inflammatory response through suppression of COX-2-mediated PGE2 production 9 and HIF-1alpha-dependent induction of Netrin-1 has been demonstrated to attenuate hypoxia-elicited inflammation at mucosal surfaces. 11 One mechanism of the anti-inflammatory effect of Netrin-1 is induction of M2 macrophage polarization through PPAR pathways and therefore promotes inflammation resolution.…”

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confidence: 99%

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Netrin‐1 and its receptor Unc5b as markers of periodontal disease

Günpınar

Meraci

Dündar

2019

J of Periodontal Research

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Objectives The aim of this present study was to evaluate the levels of Netrin‐1 and Unc5b in periodontal health and disease. Background Netrin‐1, acting via its receptor UNC5b, regulates the inflammatory response and takes apart in bone destructive diseases. Methods Samples of gingival crevicular fluid (GCF), whole saliva, and serum were taken from systemically healthy, nonsmoking 20 periodontitis , 20 gingivitis patients, and 20 periodontally healthy subjects at baseline and 4 weeks after nonsurgical periodontal treatment (NSPT). Whole‐mouth and site‐specific clinical periodontal parameters were recorded. Netrin‐1 and Unc5b levels were measured by enzyme‐linked immunosorbent assay. Data were analyzed by nonparametric tests. Results Total amount of Netrin‐1 in GCF was significantly higher in periodontitis than the others, and the levels were significantly reduced after NSPT. Salivary and serum concentrations of Netrin‐1 were significantly different among the study groups (P = .000), and NSPT significantly increased the concentration levels of both salivary and serum Netrin‐1 (P < .05). Healthy subjects had significantly lower GCF (P = .001) and conversely, higher salivary and serum levels of Unc5b than the other groups (P = .002). The GCF levels of Unc5b were significantly reduced (P < .01), and conversely, serum concentrations were significantly increased after NSPT (P < .05). GCF Netrin‐1 and Unc5b total amounts were positively correlated with clinical parameters (P < .01 and P < .05) whereas salivary Netrin‐1 and Unc5b concentrations were negatively correlated with clinical parameters (P < .01 and P < .05). Conclusions The results of this study indicate that Netrin‐1 and its receptor Unc5b may have essential roles in periodontal inflammation and those can be assumed as useful therapeutic agent to control inflammation and periodontal breakdown.

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Netrin‐1 protects blood–brain barrier (BBB) integrity after cerebral ischemia‐reperfusion by activating the Kruppel‐like factor 2 (KLF2)/occludin pathway

Li,

Liu,

Chen

et al. 2024

J Biochem & Molecular Tox

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Ischemia/reperfusion (I/R)‐induced neural damage and neuroinflammation have been associated with pathological progression during stroke. Netrin‐1 is an important member of the family of laminin‐related secreted proteins, which plays an important role in governing axon elongation. However, it is unknown whether Netrin‐1 possesses a beneficial role in stroke. Here, we employed the middle cerebral artery occlusion (MCAO) model to study the function of Netrin‐1 in alleviating brain injuries. Our results demonstrate that Netrin‐1 rescued poststroke neurological deficits and inhibited production of the inflammatory cytokines such as interleukin 6 (IL‐6) and endothelial chemokine (C‐X‐C motif) ligand 1 (Cxcl1). Importantly, Netrin‐1 protected against MCAO‐induced dysfunction of the blood–brain barrier (BBB) in mice and a reduction in the expression of the tight junction (TJ) protein occludin. Additionally, we report that Netrin‐1 could ameliorate oxygen‐glucose deprivation/reoxygenation (OGD/R)‐induced injury and prevent aggravation in endothelial monolayer permeability in bEnd.3 human brain microvascular endothelial cells (HBMVECs). Mechanistically, Netrin‐1 ameliorated OGD/R‐induced decrease in occludin and Kruppel‐like factor 2 (KLF2) in HBMVECs. Notably, silencing of KLF2 abolished the beneficial effects of Netrin‐1 in protecting endothelial permeability and occludin expression, suggesting that these effects are mediated by KLF2. In conclusion, our findings suggest that Netrin‐1 could constitute a novel therapeutic strategy for ischemic stroke.

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Netrin-1 prevents the attachment of monocytes to endothelial cells via an anti-inflammatory effect

Cited by 32 publications

References 25 publications

Netrin-1 plays a critical role in regulating capacities of epidermal stem cells upon ultraviolet-B (UV-B) irradiation

Netrin-1 plays a critical role in regulating capacities of epidermal stem cells upon ultraviolet-B (UV-B) irradiation

Netrin‐1 and its receptor Unc5b as markers of periodontal disease

Netrin‐1 protects blood–brain barrier (BBB) integrity after cerebral ischemia‐reperfusion by activating the Kruppel‐like factor 2 (KLF2)/occludin pathway

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