Amyloid-beta (25–35) peptide induces the release of pro-matrix metalloprotease 9 (pro-MMP-9) from human neutrophils

Achilli, Cesare; Ciana, Annarita; Minetti, Giampaolo

doi:10.1007/s11010-014-2178-0

Cited by 12 publications

(10 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Since MMP-9 has been implicated in TJP degradation in neuroinflammation 23 , 27 , 28 , we investigated whether MMP-9 was key in driving BBB disruption in CNS TB. Staining for MMP-9 was markedly increased around the brain endothelial cell layer at 72 hours post-stimulation (Figure S3 ).…”

Section: Resultsmentioning

confidence: 99%

Matrix metalloproteinase-9 activity and a downregulated Hedgehog pathway impair blood-brain barrier function in an in vitro model of CNS tuberculosis

Brilha

Weksler

et al. 2017

Sci Rep

View full text Add to dashboard Cite

Central nervous system tuberculosis (CNS TB) has a high mortality and morbidity associated with severe inflammation. The blood-brain barrier (BBB) protects the brain from inflammation but the mechanisms causing BBB damage in CNS TB are uncharacterized. We demonstrate that Mycobacterium tuberculosis (Mtb) causes breakdown of type IV collagen and decreases tight junction protein (TJP) expression in a co-culture model of the BBB. This increases permeability, surface expression of endothelial adhesion molecules and leukocyte transmigration. TJP breakdown was driven by Mtb-dependent secretion of matrix metalloproteinase (MMP)-9. TJP expression is regulated by Sonic hedgehog (Shh) through transcription factor Gli-1. In our model, the hedgehog pathway was downregulated by Mtb-stimulation, but Shh levels in astrocytes were unchanged. However, Scube2, a glycoprotein regulating astrocyte Shh release was decreased, inhibiting Shh delivery to brain endothelial cells. Activation of the hedgehog pathway by addition of a Smoothened agonist or by addition of exogenous Shh, or neutralizing MMP-9 activity, decreased permeability and increased TJP expression in the Mtb-stimulated BBB co-cultures. In summary, the BBB is disrupted by downregulation of the Shh pathway and breakdown of TJPs, secondary to increased MMP-9 activity which suggests that these pathways are potential novel targets for host directed therapy in CNS TB.

show abstract

Section: Resultsmentioning

confidence: 99%

Matrix metalloproteinase-9 activity and a downregulated Hedgehog pathway impair blood-brain barrier function in an in vitro model of CNS tuberculosis

Brilha

Weksler

et al. 2017

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Additionally, neutrophils in brain parenchyma may be activated by tumor necrosis TNF-α, IL-1β, and IL-8 secreted by glial cells and then releasing NETs [72][73][74], which may in turn activate glial cells and cause neuronal damage. Intraparenchymal NETs could cause neurotoxicity by disintegrating extracellular matrix, which could be caused by NETassociated proteases such as MMP-9, MPO, and NE, and activating the mitochondrial apoptosis pathway and amplifying the inflammatory process [75][76][77][78].…”

Section: Nets In Alzheimer's Disease (Ad)mentioning

confidence: 99%

The Role of Neutrophil Extracellular Traps in Central Nervous System Diseases and Prospects for Clinical Application

Guo

Zeng

Chen

2021

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

Neutrophil extracellular traps (NETs) are complexes of decondensed DNA fibers and antimicrobial peptides that are released by neutrophils and play important roles in many noninfectious diseases, such as cystic fibrosis, systemic lupus erythematosus, diabetes, and cancer. Recently, the formation of NETs has been detected in many central nervous system diseases and is thought to play different roles in the occurrence and development of these diseases. Researchers have detected NETs in acute ischemic stroke thrombi, and these NETs are thought to promote coagulation and thrombosis. NETs in ischemic brain parenchyma were identified as the cause of secondary nerve damage. High levels of NETs were also detected in grade IV glioma tissues, where NETs were involved in the proliferation and invasion of glioma cells by activating a signaling pathway. Extracellular web-like structures have also recently been observed in mice with traumatic brain injury (TBI), and it was hypothesized that NETs contribute to the development of edema after TBI. This article reviews the effect of NETs on multiple diseases that affect the CNS and explores their clinical application prospects.

show abstract

“…Neutrophils are equipped with high levels of MMP-9, stored as the inactive form pro-MMP-9. Recent data indicate that that Aβ25–35 induces the degranulation process following neutrophil activation and the massive secretion of the inactive pro-MMP-9 stored in cytoplasmic granules ( 119 ). After neutrophil stimulation, pro-MMP-9 can be converted into active MMP-9 by several of the proteases released by activated neutrophils (including NE), or by Aβ-stimulated brain cells ( 119 ).…”

Section: Intraparenchymal Netosis In Admentioning

confidence: 99%

“…Recent data indicate that that Aβ25–35 induces the degranulation process following neutrophil activation and the massive secretion of the inactive pro-MMP-9 stored in cytoplasmic granules ( 119 ). After neutrophil stimulation, pro-MMP-9 can be converted into active MMP-9 by several of the proteases released by activated neutrophils (including NE), or by Aβ-stimulated brain cells ( 119 ). MMPs are involved in the proteolysis of the extracellular matrix and can thus damage the brain parenchyma ( 120 ).…”

Section: Intraparenchymal Netosis In Admentioning

confidence: 99%

NETosis in Alzheimer’s Disease

et al. 2017

View full text Add to dashboard Cite

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by the progressive deterioration of cognitive functions. Its neuropathological features include amyloid-β (Aβ) accumulation, the formation of neurofibrillary tangles, and the loss of neurons and synapses. Neuroinflammation is a well-established feature of AD pathogenesis, and a better understanding of its mechanisms could facilitate the development of new therapeutic approaches. Recent studies in transgenic mouse models of AD have shown that neutrophils adhere to blood vessels and migrate inside the parenchyma. Moreover, studies in human AD subjects have also shown that neutrophils adhere and spread inside brain vessels and invade the parenchyma, suggesting these cells play a role in AD pathogenesis. Indeed, neutrophil depletion and the therapeutic inhibition of neutrophil trafficking, achieved by blocking LFA-1 integrin in AD mouse models, significantly reduced memory loss and the neuropathological features of AD. We observed that neutrophils release neutrophil extracellular traps (NETs) inside blood vessels and in the parenchyma of AD mice, potentially harming the blood–brain barrier and neural cells. Furthermore, confocal microscopy confirmed the presence of NETs inside the cortical vessels and parenchyma of subjects with AD, providing more evidence that neutrophils and NETs play a role in AD-related tissue destruction. The discovery of NETs inside the AD brain suggests that these formations may exacerbate neuro-inflammatory processes, promoting vascular and parenchymal damage during AD. The inhibition of NET formation has achieved therapeutic benefits in several models of chronic inflammatory diseases, including autoimmune diseases affecting the brain. Therefore, the targeting of NETs may delay AD pathogenesis and offer a novel approach for the treatment of this increasingly prevalent disease.

show abstract

Amyloid-beta (25–35) peptide induces the release of pro-matrix metalloprotease 9 (pro-MMP-9) from human neutrophils

Cited by 12 publications

References 29 publications

Matrix metalloproteinase-9 activity and a downregulated Hedgehog pathway impair blood-brain barrier function in an in vitro model of CNS tuberculosis

Matrix metalloproteinase-9 activity and a downregulated Hedgehog pathway impair blood-brain barrier function in an in vitro model of CNS tuberculosis

The Role of Neutrophil Extracellular Traps in Central Nervous System Diseases and Prospects for Clinical Application

NETosis in Alzheimer’s Disease

Contact Info

Product

Resources

About