Lysophosphatidylcholine induces apoptosis and inflammatory damage in brain microvascular endothelial cells via GPR4-mediated NLRP3 inflammasome activation

2021 ◽  
pp. 105227
Author(s):  
Tao Liu ◽  
Xuegang Wang ◽  
Feng Guo ◽  
Xiaobo Sun ◽  
Kunxiong Yuan ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Nlrp3 Inflammasome ◽  
Microvascular Endothelial Cells ◽  
Inflammasome Activation ◽  
Brain Microvascular Endothelial Cells ◽  
Inflammatory Damage ◽  
Nlrp3 Inflammasome Activation ◽  
Microvascular Endothelial

scholarly journals Knockdown of SNW1 ameliorates brain microvascular endothelial cells injury by inhibiting NLRP3 inflammasome activation

2021 ◽  
Author(s):  
Zhen Tao ◽  
Hongwei Guo ◽  
Jigang Tang ◽  
Ming Cheng
Keyword(s):  
Endothelial Cells ◽  
Western Blot ◽  
Nlrp3 Inflammasome ◽  
Cholesterol Efflux ◽  
Microvascular Endothelial Cells ◽  
Inflammasome Activation ◽  
Brain Microvascular Endothelial Cells ◽  
Nlrp3 Inflammasome Activation ◽  
Microvascular Endothelial ◽  
Nlrp3 Inflammasomes

IntroductionSNW domain containing 1 (SNW1), as a splicing factor to regulate the activity of transcription factors, has been reported to be involved in multiple disease processes, including neuroblastoma. Whereas, the latent function and concrete mechanism of SNW1 in brain microvascular endothelial cells (BMECs) have not been clarified.Material and methodsBMECs were induced by oxidized low-density lipoprotein (ox-LDL), and high fat (HF)-fed rats were established. After SNW1 knockdown or NLR family pyrin domain containing 3 (NLRP3) overexpression, SNW1 and NLRP3 expressions were monitored via RT-qPCR, Western blot, or immunohistochemistry assays. Also, cell viability, apoptosis, and cholesterol efflux were determined via CCK-8, flow cytometry, and related kits; IL-18 and IL-3 levels were also certified by ELISA kits; and NLRP3 inflammasomes and cholesterol efflux-related proteins were identified by Western blot in vitro and in vivo.ResultsWe discovered that ox-LDL or HF-feeding significantly elevated SNW1 and NLRP3 expressions, and prominently induced BMECs injury in BMECs or rat brain tissues. Subsequently, our data confirmed that SNW1 knockdown markedly accelerated cholesterol efflux and viability, and prevented apoptosis and NLRP3 inflammasomes, which also could be reversed by NLRP3 overexpression in ox-LDL-induced BMECs. In addition, we showed that SNW1 knockdown could signally induce cholesterol efflux and repress NLRP3 inflammasome activation in HF-fed rats.ConclusionsWe demonstrated that SNW1 knockdown has a great protection effect on the dysfunction of BMECs by inhibiting NLRP3. So, SNW1 might be a therapeutic target for BMECs injury.

scholarly journals Decrease of miR-19b-3p in Brain Microvascular Endothelial Cells Attenuates Meningitic Escherichia coli-Induced Neuroinflammation via TNFAIP3-Mediated NF-κB Inhibition

Pathogens ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 268 ◽  
Author(s):  
Amjad ◽  
Yang ◽  
Li ◽  
Fu ◽  
Yang ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Endothelial Cells ◽  
Negative Regulator ◽  
Microvascular Endothelial Cells ◽  
Brain Microvascular Endothelial Cells ◽  
E Coli ◽  
Inflammatory Damage ◽  
Microvascular Endothelial

Meningitic Escherichia coli can traverse the host’s blood–brain barrier (BBB) and induce severe neuroinflammatory damage to the central nervous system (CNS). During this process, the host needs to reasonably balance the battle between bacteria and brain microvascular endothelial cells (BMECs) to minimize inflammatory damage, but this quenching of neuroinflammatory responses at the BBB is unclear. MicroRNAs (miRNAs) are widely recognized as key negative regulators in many pathophysiological processes, including inflammatory responses. Our previous transcriptome sequencing revealed numbers of differential miRNAs in BMECs upon meningitic E. coli infection; we next sought to explore whether and how these miRNAs worked to modulate neuroinflammatory responses at meningitic E. coli entry of the BBB. Here, we demonstrated in vivo and in vitro that meningitic E. coli infection of BMECs significantly downregulated miR-19b-3p, which led to attenuated production of proinflammatory cytokines and chemokines via increasing the expression of TNFAIP3, a negative regulator of NF-κB signaling. Moreover, in vivo injection of miR-19b-3p mimics during meningitic E. coli challenge further aggravated the inflammatory damage to mice brains. These in vivo and in vitro findings indicate a novel quenching mechanism of the host by attenuating miR-19b-3p/TNFAIP3/NF-κB signaling in BMECs in response to meningitic E. coli, thus preventing CNS from further neuroinflammatory damage.

scholarly journals Ubiquinone Metabolism and Transcription HIF-1 Targets Pathway Are Toxicity Signature Pathways Present in Extracellular Vesicles of Paraquat-Exposed Human Brain Microvascular Endothelial Cells

2021 ◽  
Vol 22 (10) ◽  
pp. 5065
Author(s):  
Tatjana Vujić ◽  
Domitille Schvartz ◽  
Anton Iliuk ◽  
Jean-Charles Sanchez
Keyword(s):  
Endothelial Cells ◽  
Human Brain ◽  
Extracellular Vesicles ◽  
Physiological State ◽  
Microvascular Endothelial Cells ◽  
Brain Microvascular Endothelial Cells ◽  
Cell Of Origin ◽  
Functional Changes ◽  
Data Independent Acquisition ◽  
Microvascular Endothelial

Over the last decade, the knowledge in extracellular vesicles (EVs) biogenesis and modulation has increasingly grown. As their content reflects the physiological state of their donor cells, these “intercellular messengers” progressively became a potential source of biomarker reflecting the host cell state. However, little is known about EVs released from the human brain microvascular endothelial cells (HBMECs). The current study aimed to isolate and characterize EVs from HBMECs and to analyze their EVs proteome modulation after paraquat (PQ) stimulation, a widely used herbicide known for its neurotoxic effect. Size distribution, concentration and presence of well-known EV markers were assessed. Identification and quantification of PQ-exposed EV proteins was conducted by data-independent acquisition mass spectrometry (DIA-MS). Signature pathways of PQ-treated EVs were analyzed by gene ontology terms and pathway enrichment. Results highlighted that EVs exposed to PQ have modulated pathways, namely the ubiquinone metabolism and the transcription HIF-1 targets. These pathways may be potential molecular signatures of the PQ-induced toxicity carried by EVs that are reflecting their cell of origin by transporting with them irreversible functional changes.

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