Oxidized LDL activates fas-mediated endothelial cell apoptosis.

Sata, Masataka; Walsh, Kenneth

doi:10.1172/jci3531

Cited by 214 publications

(161 citation statements)

References 54 publications

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“…Others in the field have also reported apoptosis of various eukaryotic cells upon exposure to borrelia spirochetes (40)(41)(42)(43)(44). Because infection with various species of RF spirochetes can result in cerebrovascular disease in humans (3)(4)(5)(6) and experimental animals (6,7,45,46) and the major virulence factor of borrelia spirochetes, the outer membrane lipoproteins (47), is capable of causing eukaryotic cell apoptosis (41), we hypothesized that bacterial lipoproteins from B. turicatae can cause brain endothelial cell apoptosis, similar to what has been reported for oxidized human lipoproteins (48)(49)(50)(51). We investigated this possibility in mice with relapsing-remitting infection and in vitro.…”

Section: Discussionmentioning

confidence: 77%

IL-10 Prevents Apoptosis of Brain Endothelium during Bacteremia

Londoño

Carvajal

Strle

et al. 2011

The Journal of Immunology

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IL‐10 deficient mice infected with the relapsing fever bacterium Borrelia turicatae rapidly succumb to brain hemorrhage if they are unable to clear peak bacteremia. Here we investigated the protective role of IL‐10 during relapsing‐remitting bacterial infection and explored the molecular events involved in protection of brain endothelium by IL‐10. The results showed that severe endothelial cell injury leading to hemorrhage in the brain and other organs occurred in IL‐10 deficient mice during relapsing‐remitting infection. Human brain microvascular endothelial cells (HBMEC) upon exposure to whole bacteria or purified bacterial lipoprotein are rapidly killed by apoptosis and produced abundant pro‐inflammatory mediators but did not produce any IL‐10. HBMEC apoptosis during exposure to low number of bacteria was associated with down regulation of TNF and TNFAIP3 and upregulation of BAX. In contrast, exposure to high concentrations of purified outer membrane lipoprotein was associated with dramatic upregulation of FAS, FAS ligand, and the adaptor molecules RIPK1 and CFLAR. Exogenous IL‐10 reversed all the apoptotic signaling changes induced by whole bacteria or purified lipoprotein. The results indicate that IL‐10 prevent brain endothelial cell injury and point to a prominent role for bacterial lipoprotein mediated activation of different apoptosis pathways in this process.

show abstract

Section: Discussionmentioning

confidence: 77%

IL-10 Prevents Apoptosis of Brain Endothelium during Bacteremia

Londoño

Carvajal

Strle

et al. 2011

The Journal of Immunology

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show abstract

“…We recently showed that overexpression of a FADD-dominant-negative construct in a human microvascular endothelial cell line protected the cells from apoptosis following co-incubation with LPS and a protein synthesis inhibitor but that a neutralizing anti-Fas antibody did not (39). In other model systems, oxidized-LDL induced apoptosis was blocked by neutralizing mAb to FasL (45), and IL-1-induced apoptosis of Langerhans cells (46) and thyrocytes (47) was shown to involve Fas-FasL. However, blockade of the Fas-FasL apoptotic pathway by a neutralizing anti-FasL mAb did not prevent IL-1␤-or LPS-induced apoptosis in HUVECs.…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, in other model systems, oxidized LDLinduced apoptosis of endothelial cells was blocked by neutralizing mAb to Fas ligand (FasL) (45) and IL-1-induced apoptosis of Langerhans cells (46) and thyrocytes (47) was shown to involve Fas-FasL. However, blockade of the Fas-FasL apoptotic pathway by the neutralizing anti-FasL mAb, 4H9, (45,47) did not prevent IL-1␤-or LPS-induced apoptosis in HUVECs (Fig. 2).…”

Section: Il-1␤-or Lps-induced Apoptosis Does Not Involve Fas-fas Ligand-mentioning

confidence: 99%

NF-κB Activation Is Required for Human Endothelial Survival during Exposure to Tumor Necrosis Factor-α but Not to Interleukin-1β or Lipopolysaccharide

Zen¹,

Karsan²,

Stempien‐Otero³

et al. 1999

Journal of Biological Chemistry

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“…Although endothelial cells express an intact Fas pathway, death signals appear to be blocked by the coexpression of inhibitory molecules (27,28). These observations suggest that it might be possible to genetically engineer endothelial cells on grafted vessels to constitutively overexpress FasL such that host immune response would be minimized while avoiding a cytotoxic response in the endothelium.…”

Section: Fas Ligand Overexpression On Allograft Endothelium Inhibitsmentioning

confidence: 99%

Fas Ligand Overexpression on Allograft Endothelium Inhibits Inflammatory Cell Infiltration and Transplant-Associated Intimal Hyperplasia

Sata

Luo

Walsh

2001

The Journal of Immunology

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Despite recent advances in immunosuppressive therapy, accelerated coronary atherosclerosis remains a major problem in the long-term survival of transplant recipients. Chronic graft vasculopathy is believed to result from recipient inflammatory responses, and it is characterized by early mononuclear cell infiltration of the transplanted vessel. Here we show that endothelial cells can be genetically modified to overexpress functional, cell-surface Fas ligand (FasL) by adenovirus-mediated gene transfer without undergoing self-destruction. In a rodent model of transplant graft vasculopathy, endothelial overexpression of FasL attenuated T cell and macrophage infiltration at 1 wk posttransplantation. These vessels also displayed reduced neointima formation at one and 2 mo posttransplantation. These results indicate that inhibition of the early inflammatory response to allografted vessels by endothelial cell-specific overexpression of FasL may have utility in the treatment of transplant arteriosclerosis.

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Oxidized LDL activates fas-mediated endothelial cell apoptosis.

Cited by 214 publications

References 54 publications

IL-10 Prevents Apoptosis of Brain Endothelium during Bacteremia

IL-10 Prevents Apoptosis of Brain Endothelium during Bacteremia

NF-κB Activation Is Required for Human Endothelial Survival during Exposure to Tumor Necrosis Factor-α but Not to Interleukin-1β or Lipopolysaccharide

Fas Ligand Overexpression on Allograft Endothelium Inhibits Inflammatory Cell Infiltration and Transplant-Associated Intimal Hyperplasia

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