scholarly journals Apoptosis Induced by Staphylococcus aureus in Epithelial Cells Utilizes a Mechanism Involving Caspases 8 and 3

2000 ◽  
Vol 68 (5) ◽  
pp. 2998-3001 ◽  
Author(s):  
Carla A. Wesson ◽  
James Deringer ◽  
Linda E. Liou ◽  
Kenneth W. Bayles ◽  
Gregory A. Bohach ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
T Cells ◽  
Tumor Necrosis ◽  
Cellular Responses ◽  
Mammary Epithelial ◽  
Necrosis Factor Alpha ◽  
Proteolytic Cascade ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT In this study, we demonstrate that the mechanism by whichStaphylococcus aureus induces apoptosis in bovine mammary epithelial (MAC-T) cells involves caspases 8 and 3, two key components of a proteolytic cascade leading to apoptosis. In addition, internalized S. aureus induces expression of the inflammatory cytokines tumor necrosis factor alpha and interleukin-1β by MAC-T cells. These data suggest that the internalization of S. aureus could induce specific cellular responses in vivo that may ultimately impact the course of infection.

scholarly journals Peptidoglycan and Lipoteichoic Acid from Staphylococcus aureus Induce Tumor Necrosis Factor Alpha, Interleukin 6 (IL-6), and IL-10 Production in Both T Cells and Monocytes in a Human Whole Blood Model

2000 ◽  
Vol 68 (7) ◽  
pp. 3965-3970 ◽  
Author(s):  
J. E. Wang ◽  
P. F. Jørgensen ◽  
M. Almlöf ◽  
C. Thiemermann ◽  
S. J. Foster ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
T Cells ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Lipoteichoic Acid ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT We have examined the ability of peptidoglycan (PepG) and lipoteichoic acid (LTA) isolated from Staphylococcus aureusto induce the release of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and IL-10 in whole human blood and identified the cellular origins of these cytokines. Both PepG and LTA induced transient increases in TNF-α and IL-10 in plasma, with peak values at 6 and 12 h, respectively. IL-6 values increased throughout the experimental period (24 h). The TNF-α, IL-6, and IL-10 release induced by PepG and LTA was dose dependent. Only PepG was a potent inducer of TNF-α secretion. After stimulation of whole blood with PepG or LTA, very pure populations of monocytes (CD14 positive), T cells (CD2 positive), B cells (CD19 positive), and granulocytes (CD15 positive) were isolated by immunomagnetic separation and analyzed by reverse transcription-PCR for mRNA transcripts encoding TNF-α, IL-6, and IL-10. The TNF-α mRNA results were inconclusive. In contrast, PepG induced IL-6 and IL-10 mRNA accumulation in both T cells and monocytes. LTA, as well as lipopolysaccharide, induced IL-6 and IL-10 mRNA production in monocytes and possibly in T cells. Whether granulocytes and B cells produce cytokines in response to bacterial stimuli remains obscure. Blockade of the CD14 receptors with monoclonal antibodies (18D11) had no influence on the PepG-induced release of TNF-α but attenuated the LTA-induced release of the same cytokine. In conclusion, our data indicate that circulating T cells and monocytes contribute to cytokine production in sepsis caused by gram-positive bacteria.

scholarly journals Transcription Factor AP-2α Is Preferentially Cleaved by Caspase 6 and Degraded by Proteasome during Tumor Necrosis Factor Alpha-Induced Apoptosis in Breast Cancer Cells

2001 ◽  
Vol 21 (15) ◽  
pp. 4856-4867 ◽  
Author(s):  
Okot Nyormoi ◽  
Zhi Wang ◽  
Dao Doan ◽  
Maribelis Ruiz ◽  
David McConkey ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Cells ◽  
Tumor Necrosis ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Caspase 6 ◽  
Induced Apoptosis ◽  
Necrosis Factor

ABSTRACT Several reports have linked activating protein 2α (AP-2α) to apoptosis, leading us to hypothesize that AP-2α is a substrate for caspases. We tested this hypothesis by examining the effects of tumor necrosis factor alpha (TNF-α) on the expression of AP-2 in breast cancer cells. Here, we provide evidence that TNF-α downregulates AP-2α and AP-2γ expression posttranscriptionally during TNF-α-induced apoptosis. Both a general caspase antagonist (zVADfmk) and a caspase 6-preferred antagonist (zVEIDfmk) inhibited TNF-α-induced apoptosis and AP-2α downregulation. In vivo tests showed that AP-2α was cleaved by caspases ahead of the DNA fragmentation phase of apoptosis. Recombinant caspase 6 cleaved AP-2α preferentially, although caspases 1 and 3 also cleaved it, albeit at 50-fold or higher concentrations. Activated caspase 6 was detected in TNF-α-treated cells, thus confirming its involvement in AP-2α cleavage. All three caspases cleaved AP-2α at asp19 of the sequence asp-arg-his-asp (DRHD19). Mutating D19 to A19abrogated AP-2α cleavage by all three caspases. TNF-α-induced cleavage of AP-2α in vivo led to AP-2α degradation and loss of DNA-binding activity, both of which were prevented by pretreatment with zVEIDfmk. AP-2α degradation but not cleavage was inhibited in vivo by PS-431 (a proteasome antagonist), suggesting that AP-2α is degraded subsequent to cleavage by caspase 6 or caspase 6-like enzymes. Cells transfected with green fluorescent protein-tagged mutant AP-2α are resistant to TNF-α-induced apoptosis, further demonstrating the link between caspase-mediated cleavage of AP-2α and apoptosis. This is the first report to demonstrate that degradation of AP-2α is a critical event in TNF-α-induced apoptosis. Since the DRHD sequence in vertebrate AP-2 is widely conserved, its cleavage by caspases may represent an important mechanism for regulating cell survival, proliferation, differentiation, and apoptosis.

Low-dose prostacyclin has potent capillary permeability-reducing effect in cat skeletal muscle in vivo

1997 ◽  
Vol 273 (1) ◽  
pp. H200-H207 ◽  
Author(s):  
A. D. Moller ◽  
P. O. Grande
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Vascular Tone ◽  
Low Dose ◽  
Capillary Permeability ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Necrosis Factor

The dose-response effects of intravenous infusion of prostacyclin on capillary permeability (the capillary filtration coefficient technique), hydrostatic capillary pressure, transcapillary filtration, and vascular tone were analyzed in vivo on cat skeletal muscle from a normal and an increased permeability level. Increased permeability was accomplished by intra-arterial infusion of tumor necrosis factor-alpha or histamine. Permeability effects of bradykinin were also analyzed. Prostacyclin decreased capillary permeability by 8% at a dose of 0.1 ng.kg-1.min-1 and at most by 30% below control attained at 2 ng.kg-1.min-1, also with no effect on vascular tone and hydrostatic capillary pressure. The permeability increase by tumor necrosis factor-alpha and histamine (by 54 and 73%) was more than counteracted by the simultaneous infusion of prostacyclin at 2 ng.kg-1.min-1. The vasodilator effect of tumor necrosis factor-alpha was also restituted. Indomethacin (prostacyclin inhibitor)-induced increase in capillary permeability (25%) was more than restituted by prostacyclin at 2 ng.kg-1.min-1. Surprisingly, bradykinin decreased capillary permeability. We conclude that endogenous prostacyclin may be a physiological regulator of capillary permeability and that low-dose prostacyclin infusion may have clinical relevance in states of increased permeability.

scholarly journals Invariant Vα14 Chain NKT Cells Promote Plasmodium berghei Circumsporozoite Protein-Specific Gamma Interferon- and Tumor Necrosis Factor Alpha-Producing CD8+ T Cells in the Liver after Poxvirus Vaccination of Mice

2005 ◽  
Vol 73 (2) ◽  
pp. 849-858 ◽  
Author(s):  
Simone Korten ◽  
Richard J. Anderson ◽  
Carolyn M. Hannan ◽  
Eric G. Sheu ◽  
Robert Sinden ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Necrosis Factor ◽  
Plasmodium Berghei ◽  
Tumor Necrosis ◽  
Nkt Cells ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Ifn Γ ◽  
Necrosis Factor

ABSTRACT Understanding the protective mechanism in the liver induced by recombinant vaccines against the pre-erythrocytic stages of malaria is important for vaccine development. Most studies in mice have focused on splenic and peripheral blood T cells and identified gamma interferon (IFN-γ)-producing CD8+ T cells as correlates of protection, which can be induced by prime-boost vaccination with recombinant poxviruses. Invariant natural killer T (Vα14iNKT) cells can also protect against liver stage malaria, when activated, and are abundant in the liver. Since poxviruses have nonspecific immunomodulating effects, which are incompletely understood, we investigated whether recombinant poxviruses affect the protective properties of hepatic Vα14iNKT cells and thus vaccine efficacy. We show that intradermal vaccination with recombinant poxviruses activated Vα14iNKT cells and NK cells in the livers of BALB/c mice while inducing IFN-γ- and tumor necrosis factor alpha (TNF-α)-producing pre-erythrocytic stage antigen-specific CD8+ T cells. Greater numbers of hepatic Vα14iNKT cells secreted interleukin-4 than IFN-γ. Vaccinated Vα14iNKT-cell-deficient mice had lower, but still protective levels of hepatic and splenic IFN-γ+ and TNF-α+ CD8+ T cells and better protection rates later after challenge with Plasmodium berghei sporozoites. Therefore, vaccine-activated hepatic Vα14iNKT cells help in generating specific T cells but are not required for protection induced by recombinant poxviruses. Furthermore, double-positive INF-γ+/TNF-α+ CD8+ T cells were enriched in protected livers, suggesting that cells expressing both of these cytokines may be most relevant for protection.

P-selectin glycoprotein ligand-1 supports rolling on E- and P-selectin in vivo

Blood ◽  
2000 ◽  
Vol 96 (10) ◽  
pp. 3585-3591 ◽  
Author(s):  
Keith E. Norman ◽  
Andreas G. Katopodis ◽  
Gebhard Thoma ◽  
Frank Kolbinger ◽  
Anne E. Hicks ◽  
...  
Keyword(s):  
Tumor Necrosis ◽  
Necrosis Factor Alpha ◽  
Rolling Velocity ◽  
Selectin Ligand ◽  
Factor Alpha ◽  
Observable Event ◽  
Slow Rolling ◽  
Necrosis Factor

Abstract Selectin-dependent rolling is the earliest observable event in the recruitment of leukocytes to inflamed tissues. Several glycoproteins decorated with sialic acid, fucose, and/or sulfate have been shown to bind the selectins. The best-characterized selectin ligand is P-selectin glycoprotein-1 (PSGL-1) that supports P-selectin– dependent rolling in vitro and in vivo. In vitro studies have suggested that PSGL-1 may also be a ligand for E- and L-selectins. To study the in vivo function of PSGL-1, without the influence of other leukocyte proteins, the authors observed the interaction of PSGL-1–coated microspheres in mouse venules stimulated to express P- and/or E-selectin. Microspheres coated with functional recombinant PSGL-1 rolled in surgically stimulated and tumor necrosis factor alpha (TNFα)-stimulated mouse venules. P-selectin deficiency or inhibition abolished microsphere rolling in surgically and TNFα-stimulated venules, whereas E-selectin deficiency or inhibition increased microsphere rolling velocity in TNFα-stimulated venules. The results suggest that P-selectin–PSGL-1 interaction alone is sufficient to mediate rolling in vivo and that E-selectin–PSGL-1 interaction supports slow rolling.

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