scholarly journals Tumor Necrosis Factor Receptor-1 is Essential for LPS-Induced Sensitization and Tolerance to Oxygen—Glucose Deprivation in Murine Neonatal Organotypic Hippocampal Slices

2008 ◽  
Vol 29 (1) ◽  
pp. 73-86 ◽  
Author(s):  
Tina Markus ◽  
Tobias Cronberg ◽  
Corrado Cilio ◽  
Cornelis Pronk ◽  
Tadeusz Wieloch ◽  
...  
Keyword(s):  
Cell Death ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Hippocampal Slices ◽  
Neuronal Cell ◽  
Glucose Deprivation ◽  
Oxygen Glucose Deprivation ◽  
Time Interval ◽  
Necrosis Factor

Inflammation and ischemia have a synergistic damaging effect in the immature brain. The role of tumor necrosis factor (TNF) receptors 1 and 2 in lipopolysaccharide (LPS)-induced sensitization and tolerance to oxygen—glucose deprivation (OGD) was evaluated in neonatal murine hippocampal organotypic slices. Hippocampal slices from balb/c, C57BL/6 TNFR1−/-, TNFR2−/-, and wild-type (WT) mice obtained at P6 were grown in vitro for 9 days. Preexposure to LPS immediately before OGD increased propidium iodide-determined cell death in regions CA1, CA3, and dentate gyrus from 4 up to 48 h after OGD ( P < 0.001). Extending the time interval between LPS exposure and OGD to 72 h resulted in tolerance, that is reduced neuronal cell death after OGD ( P < 0.05). Slices from TNFR1−/- mice showed neither LPS-induced sensitization nor LPS-induced tolerance to OGD, whereas both effects were present in slices from TNFR2−/- and WT mice. Cytokine secretion (TNFα and interleukin-6) during LPS exposure was decreased in TNFR1−/- slices and increased in TNFR2−/- as compared with WT slices. We conclude that LPS induces sensitization or tolerance to OGD depending on the time interval between exposure to LPS and OGD in murine hippocampal slice cultures. Both paradigms are dependent on signaling through TNFR1.

Tumor necrosis factor attenuates prion protein-deficient neuronal cell death by increases in anti-apoptotic Bcl-2 family proteins

2003 ◽  
Vol 310 (3) ◽  
pp. 725-729 ◽  
Author(s):  
Akikazu Sakudo ◽  
Deug-Chan Lee ◽  
Keiichi Saeki ◽  
Yoshitsugu Matsumoto ◽  
Shigeyoshi Itohara ◽  
...  
Keyword(s):  
Cell Death ◽  
Tumor Necrosis Factor ◽  
Prion Protein ◽  
Tumor Necrosis ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Necrosis Factor

scholarly journals Membrane Tumor Necrosis Factor (TNF) Induced Cooperative Signaling of TNFR60 and TNFR80 Favors Induction of Cell Death Rather Than Virus Production in HIV-infected T Cells

1997 ◽  
Vol 185 (1) ◽  
pp. 81-90 ◽  
Author(s):  
Janis K. Lazdins ◽  
Matthias Grell ◽  
Maja R. Walker ◽  
Kathie Woods-Cook ◽  
Peter Scheurich ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Death ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Dominant Role ◽  
Membrane Receptors ◽  
Specific Antibodies ◽  
Necrosis Factor ◽  
Cooperative Signaling

Tumor necrosis factor (TNF) and lymphotoxin (LT) are highly pleiotropic cytokines that play a central role in regulating HIV-1 replication. These cytokines express their activities through two membrane receptors, TNFR60 (p55-60) and TNFR80 (p75-80). In the present study we have demonstrated by means of antagonistic and agonistic receptor-specific antibodies that in latently infected lymphocytic (ACH-2) cells the TNFR60 plays a dominant role in signaling HIV production, although selective activation of TNFR80 by receptor-specific antibodies can also induce HIV production. Unexpectedly, when both TNFRs were activated simultaneously by agonistic antibodies or coculture with cells expressing a noncleavable membrane form of TNF, HIV production was downregulated and induction of cell death was enhanced in ACH-2 cells. More relevant, in vitro HIV-infected peripheral blood lymphocytes cocultured with cells expressing membrane TNF underwent rapid induction of apoptosis with a subsequent reduced HIV production of these lymphocytes cultures. This was not observed with HIV-infected lymphocytes treated with soluble TNF. These data provide evidence for the differential trigger potential of membrane versus soluble TNF and show that TNFR80 is an important modulator of TNF responsiveness of HIV-infected T cells via cooperative signaling with TNFR60.

scholarly journals The Death Domain Kinase RIP Protects Thymocytes from Tumor Necrosis Factor Receptor Type 2–induced Cell Death

2002 ◽  
Vol 196 (1) ◽  
pp. 15-26 ◽  
Author(s):  
Nicole Cusson ◽  
Sarah Oikemus ◽  
Elizabeth D. Kilpatrick ◽  
Leslie Cunningham ◽  
Michelle Kelliher
Keyword(s):  
T Cells ◽  
Cell Death ◽  
T Cell ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Receptor ◽  
Receptor Activation ◽  
Death Domain ◽  
Necrosis Factor

Fas and the tumor necrosis factor receptor (TNFR)1 regulate the programmed cell death of lymphocytes. The death domain kinase, receptor interacting protein (rip), is recruited to the TNFR1 upon receptor activation. In vitro, rip−/− fibroblasts are sensitive to TNF-induced cell death due to an impaired nuclear factor κB response. Because rip−/− mice die at birth, we were unable to examine the effects of a targeted rip mutation on lymphocyte survival. To address the contribution of RIP to immune homeostasis, we examined lethally irradiated mice reconstituted with rip−/− hematopoietic precursors. We observed a decrease in rip−/− thymocytes and T cells in both wild-type C57BL/6 and recombination activating gene 1−/− irradiated hosts. In contrast, the B cell and myeloid lineages are unaffected by the absence of rip. Thus, the death domain kinase rip is required for T cell development. Unlike Fas-associated death domain, rip does not regulate T cell proliferation, as rip−/− T cells respond to polyclonal activators. However, rip-deficient mice contain few viable CD4+ and CD8+ thymocytes, and rip−/− thymocytes are sensitive to TNF-induced cell death. Surprisingly, the rip-associated thymocyte apoptosis was not rescued by the absence of TNFR1, but appears to be rescued by an absence of TNFR2. Taken together, this study implicates RIP and TNFR2 in thymocyte survival.

scholarly journals The Interaction between Tumor Necrosis Factor-Like Weak Inducer of Apoptosis and its Receptor Fibroblast Growth Factor-Inducible 14 Promotes the Recruitment of Neutrophils into the Ischemic Brain

2010 ◽  
Vol 30 (6) ◽  
pp. 1147-1156 ◽  
Author(s):  
Woldeab B Haile ◽  
Ramiro Echeverry ◽  
Jialing Wu ◽  
Manuel Yepes
Keyword(s):  
Cerebral Ischemia ◽  
Growth Factor ◽  
Tumor Necrosis Factor ◽  
Fibroblast Growth Factor ◽  
Tumor Necrosis ◽  
Glucose Deprivation ◽  
Fibroblast Growth ◽  
Ischemic Tissue ◽  
Necrosis Factor

Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor fibroblast growth factor-inducible 14 (Fn14) are expressed in endothelial cells and perivascular astrocytes. Here, we show that TWEAK induces a dose-dependent increase in the expression of the chemokine monocyte chemoattractant protein-1 (MCP-1) in astrocytes, and that this effect is mediated by its interaction with Fn14 via nuclear factor-κB pathway activation. Exposure to oxygen-glucose deprivation (OGD) conditions increases TWEAK and Fn14 mRNA expression in wild-type (Wt) astrocytic cultures. Likewise, incubation under OGD conditions induces the expression of MCP-1 in Wt astrocytes but not in astrocytes deficient on either TWEAK (TWEAK−/−) or Fn14 (Fn14−/−). We also found that TWEAK induces the passage of neutrophils to the abluminal side of an in vitro model of the blood–brain barrier. Our earlier studies indicate that cerebral ischemia increases the expression of TWEAK and Fn14 in the endothelial cell-basement membrane-astrocyte interface. Here, we report that middle cerebral artery occlusion increases the expression of MCP-1 and the recruitment of neutrophils into the ischemic tissue in Wt but not in TWEAK−/− or Fn14−/− mice. These novel results indicate that during cerebral ischemia, the interaction between TWEAK and Fn14 leads to the recruitment of leukocytes into the ischemic tissue.

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