scholarly journals Porphyromonas gingivalis Induces Proinflammatory Cytokine Expression Leading to Apoptotic Death through the Oxidative Stress/NF-κB Pathway in Brain Endothelial Cells

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3033
Author(s):  
Vichuda Charoensaensuk ◽  
Yen-Chou Chen ◽  
Yun-Ho Lin ◽  
Keng-Liang Ou ◽  
Liang-Yo Yang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Death ◽  
Proinflammatory Cytokine ◽  
Ros Production ◽  
Brain Endothelial Cell ◽  
Brain Endothelial Cells ◽  
Tnf Α ◽  
Primary Mouse ◽  
Endothelial Cell Death ◽  
The Impact

Porphyromonas gingivalis, a periodontal pathogen, has been proposed to cause blood vessel injury leading to cerebrovascular diseases such as stroke. Brain endothelial cells compose the blood-brain barrier that protects homeostasis of the central nervous system. However, whether P. gingivalis causes the death of endothelial cells and the underlying mechanisms remain unclear. This study aimed to investigate the impact and regulatory mechanisms of P. gingivalis infection in brain endothelial cells. We used bEnd.3 cells and primary mouse endothelial cells to assess the effects of P. gingivalis on endothelial cells. Our results showed that infection with live P. gingivalis, unlike heat-killed P. gingivalis, triggers brain endothelial cell death by inducing cell apoptosis. Moreover, P. gingivalis infection increased intracellular reactive oxygen species (ROS) production, activated NF-κB, and up-regulated the expression of IL-1β and TNF-α. Furthermore, N-acetyl-L-cysteine (NAC), a most frequently used antioxidant, treatment significantly reduced P. gingivalis-induced cell apoptosis and brain endothelial cell death. The enhancement of ROS production, NF-κB p65 activation, and proinflammatory cytokine expression was also attenuated by NAC treatment. The impact of P. gingivalis on brain endothelial cells was also confirmed using adult primary mouse brain endothelial cells (MBECs). In summary, our results showed that P. gingivalis up-regulates IL-1β and TNF-α protein expression, which consequently causes cell death of brain endothelial cells through the ROS/NF-κB pathway. Our results, together with the results of previous case-control studies and epidemiologic reports, strongly support the hypothesis that periodontal infection increases the risk of developing cerebrovascular disease.

scholarly journals Vibrio vulnificus Hemolysin Induces TNF-α Independent ROS Production by Primary Murine Macrophages

2021 ◽  
Author(s):  
Yong-Liang Lou ◽  
Dan-Li Xie ◽  
Xian-Hui Huang ◽  
Meng-Meng Zheng ◽  
Ting Zhang ◽  
...  
Keyword(s):  
Cell Death ◽  
Vibrio Vulnificus ◽  
Opportunistic Pathogen ◽  
Cytolytic Activity ◽  
Host Cells ◽  
Ros Generation ◽  
Ros Production ◽  
Host Cell Apoptosis ◽  
Tnf Α ◽  
The Impact

Abstract BackgroundVibrio vulnificus (V. vulnificus) is a gram-negative opportunistic pathogen that causes lethal infections in humans. Vibrio vulnificus hemolysin (VVH) is a key virulence factor that exhibits strong hemolytic and cytolytic activities and contributes to the pathogen's invasion, vasodilatation, and septic shock. Most of the studies so far have focused on VVH's cytolytic activity against cell lines derived from host cells. However, the cytolytic activity of VVH on primary macrophages is still unclear. In addition, although it is known that VVH induces host cell apoptosis via triggering ROS production, the impact of VVH on host immune response has not been fully understood. This study aimed to investigate the role of VVH-induced TNF-α expression and ROS production in the absence of apoptosis of murine primary macrophages and related signaling pathways using FACS, DCFH-DA, real-time PCR, and western blotting. ResultsThe results showed that murine primary macrophages from different organs displayed differential sensitivities towards VVH-induced cell death. Liver Kupffer cells, splenic macrophages, and BMMfs were more sensitive to VVH-induced cytotoxicity, while alveolar macrophages, lung interstitial macrophages, and lung neutrophils were resistant to VVH-induced cell death. Besides, we found that a low dose of VVH, which did not induce apoptosis in murine primary macrophages, could induce apoptosis independent TNF-α expression and ROS generation. Such ROS production in macrophages could be further blocked by inhibiting p38-MAPKs or NFκB activation but was not affected by knockout of TNF-α. ConclusionsVVH produced cytotoxicity in macrophages, an apoptosis-independent TNF-α expression, and ROS production, which provides insight into the mechanism underlying the crosstalk between VVH-induced inflammation and oxidative stress.

scholarly journals Role of thromboxane in retinal microvascular degeneration in oxygen-induced retinopathy

2001 ◽  
Vol 90 (6) ◽  
pp. 2279-2288 ◽  
Author(s):  
Martin H. Beauchamp ◽  
Ana Katherine Martinez-Bermudez ◽  
Fernand Gobeil ◽  
Anne Marilise Marrache ◽  
Xin Hou ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Death ◽  
Endothelial Cell ◽  
Oxidant Stress ◽  
Microvascular Endothelial Cell ◽  
Oxygen Induced Retinopathy ◽  
Rat Pups ◽  
Endothelial Cell Death ◽  
Peroxidation Product ◽  
Synthase Inhibitor

Microvascular degeneration is an important event in oxygen-induced retinopathy (OIR), a model of retinopathy of prematurity. Because oxidant stress abundantly generates thromboxane A2(TxA2), we tested whether TxA2plays a role in retinal vasoobliteration of OIR and contributes to such vascular degeneration by direct endothelial cytotoxicity. Hyperoxia-induced retinal vasoobliteration in rat pups (80% O2exposure from postnatal days 5–14) was associated with increased TxB2generation and was significantly prevented by TxA2synthase inhibitor CGS-12970 (10 mg · kg−1· day−1) or TxA2-receptor antagonist CGS-22652 (10 mg · kg−1· day−1). TxA2mimetics U-46619 (EC5050 nM) and I-BOP (EC505 nM) caused a time- and concentration-dependent cell death of neuroretinovascular endothelial cells from rats as well as newborn pigs but not of smooth muscle and astroglial cells; other prostanoids did not cause cell death. The peroxidation product 8-iso-PGF2, which is generated in OIR, stimulated TxA2formation by endothelial cells and triggered cell death; these effects were markedly diminished by CGS-12970. TxA2-dependent neuroretinovascular endothelial cell death was mostly by necrosis and to a lesser extent by apoptosis. The data identify an important role for TxA2in vasoobliteration of OIR and unveil a so far unknown function for TxA2in directly triggering neuroretinal microvascular endothelial cell death. These effects of TxA2might participate in other ischemic neurovascular injuries.

NGP1-01, a multi-targeted polycyclic cage amine, attenuates brain endothelial cell death in iron overload conditions

2012 ◽  
Vol 1489 ◽  
pp. 133-139 ◽  
Author(s):  
J.A. Lockman ◽  
W.J. Geldenhuys ◽  
M.R. Jones-Higgins ◽  
J.D. Patrick ◽  
D.D. Allen ◽  
...  
Keyword(s):  
Cell Death ◽  
Endothelial Cell ◽  
Iron Overload ◽  
Brain Endothelial Cell ◽  
Endothelial Cell Death

scholarly journals Porphyromonas gingivalis Differentially Modulates Cell Death Profile in Ox-LDL and TNF-α Pre-Treated Endothelial Cells

PLoS ONE ◽  
2016 ◽  
Vol 11 (4) ◽  
pp. e0154590 ◽  
Author(s):  
Isaac Maximiliano Bugueno ◽  
Yacine Khelif ◽  
Narendra Seelam ◽  
David-Nicolas Morand ◽  
Henri Tenenbaum ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Death ◽  
Porphyromonas Gingivalis ◽  
Tnf Α

Enhanced mtDNA repair capacity protects pulmonary artery endothelial cells from oxidant-mediated death

2002 ◽  
Vol 283 (1) ◽  
pp. L205-L210 ◽  
Author(s):  
Allison W. Dobson ◽  
Valentina Grishko ◽  
Susan P. LeDoux ◽  
Mark R. Kelley ◽  
Glenn L. Wilson ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Death ◽  
Dna Repair ◽  
Trypan Blue Exclusion ◽  
Mt Dna ◽  
Repair Capacity ◽  
Mtdna Damage ◽  
Pulmonary Arterial ◽  
Selective Enhancement ◽  
The Impact

In rat cultured pulmonary arterial (PA), microvascular, and venous endothelial cells (ECs), the rate of mitochondrial (mt) DNA repair is predictive of the severity of xanthine oxidase (XO)-induced mtDNA damage and the sensitivity to XO-mediated cell death. To examine the importance of mtDNA damage and repair more directly, we determined the impact of mitochondrial overexpression of the DNA repair enzyme, Ogg1, on XO-induced mtDNA damage and cell death in PAECs. PAECs were transiently transfected with an Ogg1-mitochondrial targeting sequence construct. Mitochondria-selective overexpression of the transgene product was confirmed microscopically by the observation that immunoreactive Ogg1 colocalized with a mitochondria-specific tracer and, with an oligonucleotide cleavage assay, by a selective enhancement of mitochondrial Ogg1 activity. Overexpression of Ogg1 protected against both XO-induced mtDNA damage, determined by quantitative Southern analysis, and cell death as assessed by trypan blue exclusion and MTS assays. These findings show that mtDNA damage is a direct cause of cell death in XO-treated PAECs.

scholarly journals Delivering Minocycline into Brain Endothelial Cells with Liposome-Based Technology

2012 ◽  
Vol 32 (6) ◽  
pp. 983-988 ◽  
Author(s):  
Changhong Xing ◽  
Tatyana Levchenko ◽  
Shuzhen Guo ◽  
Monique Stins ◽  
Vladimir P Torchilin ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Tumor Necrosis ◽  
Proof Of Concept ◽  
Brain Endothelial Cells ◽  
Cerebral Endothelium ◽  
Low Concentrations ◽  
Tnf Α ◽  
Factor Α ◽  
Very High ◽  
Necrosis Factor

Minocycline has been proposed as a way to blunt neurovascular injury from matrix metalloproteinases (MMPs) during stroke. However, recent clinical trials suggest that high levels of minocycline may have deleterious side-effects. Here, we showed that very high minocycline concentrations damage endothelial cells via calpain/caspase pathways. To alleviate this potential cytotoxicity, we encapsulated minocycline in liposomes. Low concentrations of minocycline could not reduce tumor necrosis factor α (TNF α)-induced MMP-9 release from endothelial cells. But low concentrations of minocycline-loaded liposomes significantly reduced TNF α-induced MMP-9 release. This study provides proof-of-concept that liposomes may be used to deliver lower levels of minocycline for targeting MMPs in cerebral endothelium.

scholarly journals PSVI-13 Anti-inflammatory effects of polyphenol-rich red osier dogwood extracts in Caco-2 mono- and Caco-2/EA.hy926 co-culture models

2019 ◽  
Vol 97 (Supplement_3) ◽  
pp. 211-212
Author(s):  
Hua Zhang ◽  
Yuhuan Chen ◽  
Lili Mats ◽  
Qianru Hui ◽  
Rong Tsao ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Phenolic Compounds ◽  
Inflammatory Responses ◽  
Cell Model ◽  
Circulation System ◽  
Systemic Diseases ◽  
Potential Health ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
The Impact

Abstract An impaired intestinal barrier function results in aggravating inflammatory response at a systemic scale, eventually leading to rising risk for systemic diseases (e.g., muscle myopathy and vascular disorders). In the present study, the impact of intake polyphenol-rich red osier dogwood extracts (RWE) on the inflammation of endothelial cells was exploited. A strong anti-inflammatory activity of RWE was found to suppress the expression of pro-inflammatory mediators (e.g., IL-8, TNF-α, IL-6, and ICAM) in the inflamed intestinal epithelial cell model. Furthermore, the intestinal transported RWE derived phenolic compounds was shown to protect the endothelial cells against both oxidative and inflammatory damages in a Caco-2/EA.hy926 co-culture cell model. Their protective activities in EA.hy926 was found to be strongly associated with intestinal absorption efficiency. The accumulation of transported rutin and unknown monoglyceride quercetin from RWE were identified across the Caco-2 BBe1 monolayer by HPLC up to 24 h. The highest concentration of transported rutin and monoglyceride quercetin derived from RWE were detected as 2.0 ± 0.22 µg/mL and 0.5 ± 0.08 µg/mL in the basolateral compartment after 12 h and 24 h of incubation, respectively. Profound anti-inflammatory effects of RWE derived polyphenols was observed to suppress pro-inflammatory mediator expression, including IL-8, TNF-α, IL-6, ICAM, VCAM and Cox2, in the TNF-α or oxidized low-density lipoprotein (oxLDL)-induced basolateral EA.hy926 cells (co-culture model). Moreover, we observed a significant inhibitory effect of the transported RWE on oxLDL-induced inflammation after 6 h incubation rather than 24 h, indicating the potential health benefits of RWE is determined by its bioavailability. Results of this study demonstrated that phenolic compounds derived from RWE could be delivered into the circulation system to mitigate inflammatory responses thereby being a promising dietary agent for preventing systemic diseases (e.g., cardiovascular diseases in humans and white stripping/woody meat in broiler chickens).

scholarly journals Interaction between Endothelial Protein C Receptor and Intercellular Adhesion Molecule 1 to Mediate Binding of Plasmodium falciparum -Infected Erythrocytes to Endothelial Cells

mBio ◽  
2016 ◽  
Vol 7 (4) ◽  
Author(s):  
Marion Avril ◽  
Maria Bernabeu ◽  
Maxwell Benjamin ◽  
Andrew Jay Brazier ◽  
Joseph D. Smith
Keyword(s):  
Endothelial Cells ◽  
Cerebral Malaria ◽  
Intercellular Adhesion Molecule ◽  
Brain Endothelial Cells ◽  
Endothelial Protein C Receptor ◽  
Intercellular Adhesion Molecule 1 ◽  
Cd36 Expression ◽  
Tnf Α ◽  
Group A ◽  
The Brain

ABSTRACT Intercellular adhesion molecule 1 (ICAM-1) and the endothelial protein C receptor (EPCR) are candidate receptors for the deadly complication cerebral malaria. However, it remains unclear if Plasmodium falciparum parasites with dual binding specificity are involved in cytoadhesion or different parasite subpopulations bind in brain microvessels. Here, we investigated this issue by studying different subtypes of ICAM-1-binding parasite lines. We show that two parasite lines expressing domain cassette 13 (DC13) of the P. falciparum erythrocyte membrane protein 1 (PfEMP1) family have dual binding specificity for EPCR and ICAM-1 and further mapped ICAM-1 binding to the first DBLβ domain following the PfEMP1 head structure in both proteins. As PfEMP1 head structures have diverged between group A (EPCR binders) and groups B and C (CD36 binders), we also investigated how ICAM-1-binding parasites with different coreceptor binding traits influence P. falciparum -infected erythrocyte binding to endothelial cells. Whereas levels of binding to tumor necrosis factor alpha (TNF-α)-stimulated endothelial cells from the lung and brain by all ICAM-1-binding parasite lines increased, group A (EPCR and ICAM-1) was less dependent than group B (CD36 and ICAM-1) on ICAM-1 upregulation. Furthermore, both group A DC13 parasite lines had higher binding levels to brain endothelial cells (a microvascular niche with limited CD36 expression). This study shows that ICAM-1 is a coreceptor for a subset of EPCR-binding parasites and provides the first evidence of how EPCR and ICAM-1 interact to mediate parasite binding to both resting and TNF-α-activated primary brain and lung endothelial cells. IMPORTANCE Cerebral malaria is a severe neurological complication of P. falciparum infection associated with infected erythrocyte (IE) binding in cerebral vessels. Yet little is known about the mechanisms by which parasites adhere in the brain or other microvascular sites. Here, we studied parasite lines expressing group A DC13-containing PfEMP1 variants, a subset that has previously been shown to have high brain cell- and other endothelial cell-binding activities. We show that DC13-containing PfEMP1 variants have dual EPCR- and ICAM-1-binding activities and that both receptors are involved in parasite adherence to lung and brain endothelial cells. As both EPCR and ICAM-1 are implicated in cerebral malaria, these findings suggest the possibility that parasites with dual binding activities are involved in parasite sequestration to microvascular beds with low CD36 expression, such as the brain, and we urge more research into the multiadhesive properties of PfEMP1 variants.

scholarly journals Neuregulin-1 Signaling in Brain Endothelial Cells

2008 ◽  
Vol 29 (1) ◽  
pp. 39-43 ◽  
Author(s):  
Josephine Lok ◽  
S Pablo Sardi ◽  
Shuzhen Guo ◽  
Elaine Besancon ◽  
Duy M Ha ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Death ◽  
Protein Expression ◽  
Human Brain ◽  
Microvascular Endothelial Cells ◽  
Brain Microvascular Endothelial Cells ◽  
Brain Endothelial Cells ◽  
Neuregulin 1 ◽  
Multiple Functions ◽  
Mrna And Protein Expression

Neuregulin-1 (NRG1) signaling has multiple functions in neurons and glia. The data in this study show that NRG1 may also possess significant signaling and cytoprotective properties in human brain microvascular endothelial cells (BMECs). Neuregulin-1 mRNA and protein expression are present in these cells, and NRG1 receptors erbB2 and erbB3 are phosphorylated in response to NRG1. Neuregulin-1 triggers clear biologic responses in BMECs—elevated phospho-Akt levels, increased ring formation in a Matrigel assay, and decreased cell death after oxidative injury with H2O2. These data suggest that NRG1 signaling is functional and cytoprotective in BMECs.

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