scholarly journals Triglyceride-rich lipoproteins prevent septic death in rats.

1995 ◽  
Vol 182 (1) ◽  
pp. 267-272 ◽  
Author(s):  
T E Read ◽  
C Grunfeld ◽  
Z L Kumwenda ◽  
M C Calhoun ◽  
J P Kane ◽  
...  
Keyword(s):  
Lipid Emulsion ◽  
Tumor Necrosis ◽  
Lethal Dose ◽  
Cecal Ligation ◽  
Serum Levels ◽  
Cecal Ligation And Puncture ◽  
Gram Negative ◽  
Necrosis Factor ◽  
Serum Tumor Necrosis

Triglyceride-rich lipoproteins bind and inactive bacterial endotoxin in vitro and prevent death when given before a lethal dose of endotoxin in animals. However, lipoproteins have not yet been demonstrated to improve survival in polymicrobial gram-negative sepsis. We therefore tested the ability of triglyceride-rich lipoproteins to prevent death after cecal ligation and puncture (CLP) in rats. Animals were given bolus infusions of either chylomicrons (1 g triglyceride/kg per 4 h) or an equal volume of saline for 28 h after CLP. Chylomicron infusions significantly improved survival (measured at 96 h) compared with saline controls (80 vs 27%, P < or = 0.03). Chylomicron infusions also reduced serum levels of endotoxin, measured 90 min (26 +/- 3 vs 136 +/- 51 pg/ml, mean +/- SEM, P < or = 0.03) and 6 h (121 +/- 54 vs 1,026 +/- 459 pg/ml, P < or = 0.05) after CLP. The reduction in serum endotoxin correlated with a reduction in serum tumor necrosis factor, measured 6 h after CLP (0 +/- 0 vs 58 +/- 24 pg/ml, P < or = 0.03), suggesting that chylomicrons improve survival in this model by limiting macrophage exposure to endotoxin and thereby reducing secretion of inflammatory cytokines. Infusions of a synthetic triglyceride-rich lipid emulsion (Intralipid; KabiVitrum, Inc., Alameda, CA) (1 g triglyceride/kg) also significantly improved survival compared with saline controls (71 vs 27%, P < or = 0.03). These data demonstrate that triglyceride-rich lipoproteins can protect animals from lethal polymicrobial gram-negative sepsis.

scholarly journals A Study of Cecal Ligation and Puncture-Induced Sepsis in Tissue-Specific Tumor Necrosis Factor Receptor 1-Deficient Mice

2019 ◽  
Vol 10 ◽  
Author(s):  
Jolien Vandewalle ◽  
Sophie Steeland ◽  
Sara Van Ryckeghem ◽  
Melanie Eggermont ◽  
Elien Van Wonterghem ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Cecal Ligation ◽  
Tumor Necrosis Factor Receptor ◽  
Cecal Ligation And Puncture ◽  
Tissue Specific ◽  
Specific Tumor ◽  
Deficient Mice ◽  
Necrosis Factor

scholarly journals Lipopolysaccharide- TLR-4 Axis regulates Osteoclastogenesis independent of RANKL/RANK signaling

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Mohammed S. AlQranei ◽  
Linda T. Senbanjo ◽  
Hanan Aljohani ◽  
Therwa Hamza ◽  
Meenakshi A. Chellaiah
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Osteoclast Differentiation ◽  
Bone Diseases ◽  
Raw 264.7 Cells ◽  
Gram Negative ◽  
Tnf Α ◽  
Necrosis Factor ◽  
In Cells

Abstract Background Lipopolysaccharide (LPS) is an endotoxin and a vital component of gram-negative bacteria’s outer membrane. During gram-negative bacterial sepsis, LPS regulates osteoclast differentiation and activity, in addition to increasing inflammation. This study aimed to investigate how LPS regulates osteoclast differentiation of RAW 264.7 cells in vitro. Results Herein, we revealed that RAW cells failed to differentiate into mature osteoclasts in vitro in the presence of LPS. However, differentiation occurred in cells primed with receptor activator of nuclear factor-kappa-Β ligand (RANKL) for 24 h and then treated with LPS for 48 h (henceforth, denoted as LPS-treated cells). In cells treated with either RANKL or LPS, an increase in membrane levels of toll-like receptor 4 (TLR4) receptor was observed. Mechanistically, an inhibitor of TLR4 (TAK-242) reduced the number of osteoclasts as well as the secretion of tumor necrosis factor (TNF)-α in LPS-treated cells. RANKL-induced RAW cells secreted a very basal level TNF-α. TAK-242 did not affect RANKL-induced osteoclastogenesis. Increased osteoclast differentiation in LPS-treated osteoclasts was not associated with the RANKL/RANK/OPG axis but connected with the LPS/TLR4/TNF-α tumor necrosis factor receptor (TNFR)-2 axis. We postulate that this is because TAK-242 and a TNF-α antibody suppress osteoclast differentiation. Furthermore, an antibody against TNF-α reduced membrane levels of TNFR-2. Secreted TNF-α appears to function as an autocrine/ paracrine factor in the induction of osteoclastogenesis independent of RANKL. Conclusion TNF-α secreted via LPS/TLR4 signaling regulates osteoclastogenesis in macrophages primed with RANKL and then treated with LPS. Our findings suggest that TLR4/TNF-α might be a potential target to suppress bone loss associated with inflammatory bone diseases, including periodontitis, rheumatoid arthritis, and osteoporosis.

Tissue Tumor Necrosis Factor mRNA Expression Following Cecal Ligation and Puncture or Intraperitoneal Injection of Endotoxin

1994 ◽  
Vol 56 (6) ◽  
pp. 549-555 ◽  
Author(s):  
Dimitri J. Hadjiminas ◽  
Kelly M. McMasters ◽  
James C. Peyton ◽  
William G. Cheadle
Keyword(s):  
Tumor Necrosis Factor ◽  
Mrna Expression ◽  
Intraperitoneal Injection ◽  
Tumor Necrosis ◽  
Cecal Ligation ◽  
Cecal Ligation And Puncture ◽  
Tissue Tumor ◽  
Tumor Necrosis Factor Mrna ◽  
Necrosis Factor

scholarly journals Protective Effects of Polydatin on Septic Lung Injury in Mice via Upregulation of HO-1

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Xiao-hui Li ◽  
Xia Gong ◽  
Li Zhang ◽  
Rong Jiang ◽  
Hong-zhong Li ◽  
...  
Keyword(s):  
Lung Injury ◽  
Tumor Necrosis ◽  
Cecal Ligation ◽  
Protective Effects ◽  
Protein Expressions ◽  
Cox 2 ◽  
Oxide Synthase ◽  
Necrosis Factor ◽  
Serum Tumor Necrosis ◽  
Inducible Nitric Oxide

The present study was carried out to investigate the effects and mechanisms of polydatin (PD) in septic mice. The model of cecal ligation and puncture (CLP-)induced sepsis was employed. Pretreatment of mice with PD (15, 45, and 100 mg/kg) dose-dependently reduced sepsis-induced mortality and lung injury, as indicated by alleviated lung pathological changes and infiltration of proteins and leukocytes. In addition, PD inhibited CLP-induced serum tumor necrosis factor-α(TNF-α) and interleukin-6 (IL-6) production, lung cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase isoform (iNOS) protein expressions and NF-κB activation. Notably, PD upregulated the expression and activity of heme oxygenase (HO-)1 in lung tissue of septic mice. Further, the protective effects of PD on sepsis were abrogated by ZnPP IX, a specific HO-1 inhibitor. These findings indicated that PD might be an effective antisepsis drug.

scholarly journals Differential Tumor Necrosis Factor Alpha Expression and Release from Peritoneal Mouse Macrophages In Vitro in Response to Proliferating Gram-Positive versus Gram-Negative Bacteria

2000 ◽  
Vol 68 (8) ◽  
pp. 4422-4429 ◽  
Author(s):  
Wei Cui ◽  
David C. Morrison ◽  
Richard Silverstein
Keyword(s):  
Tumor Necrosis ◽  
Necrosis Factor Alpha ◽  
Gram Negative ◽  
E Coli ◽  
Tnf Α ◽  
Mouse Macrophages ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT Viable Escherichia coli and Staphylococcus aureus bacteria elicited markedly different in vitro tumor necrosis factor alpha (TNF-α) responses when placed in coculture with peritoneal murine macrophages. These include quantitative differences in TNF-α mRNA expression and corresponding protein product secretion as well as kinetic differences in the profiles of the TNF-α responses. Further, lipopolysaccharide (from E. coli) is a major contributing factor to these differences, as revealed by comparative experiments with endotoxin-responsive (C3Heb/FeJ) and endotoxin-hyporesponsive (C3H/HeJ) macrophages. Nevertheless, the eventual overall magnitude of the TNF-α secretion of macrophages in response to S. aureus was at least equivalent to that observed with E. coli, while appearing at time periods hours later than the E. coli-elicited TNF-α response. Both the magnitude and kinetic profile of the TNF-α responses were found to be relatively independent of the rate of bacterial proliferation, at least to the extent that similar results were observed with both viable and paraformaldehyde-killed microbes. Nevertheless, S. aureus treated in culture with the carbapenem antibiotic imipenem manifests markedly altered profiles of TNF-α response, with the appearance of an early TNF-α peak not seen with viable organisms, a finding strikingly similar to that recently reported by our laboratory from in vivo studies (R. Silverstein, J. G. Wood, Q. Xue, M. Norimatsu, D. L. Horn, and D. C. Morrison, Infect. Immun. 68:2301–2308, 2000). In contrast, imipenem treatment of E. coli-cocultured macrophages does not significantly alter the observed TNF-α response either in vitro or in vivo. In conclusion, our data support the concept that the host inflammatory response of cultured mouse macrophages in response to viable gram-positive versus gram-negative microbes exhibits distinctive characteristics and that these distinctions are, under some conditions, altered on subsequent bacterial killing, depending on the mode of killing. Of potential importance, these distinctive in vitro TNF-α profiles faithfully reflect circulating levels of TNF-α in infected mice. These results suggest that coculture of peritoneal macrophages with viable versus antibiotic-killed bacteria and subsequent assessment of cytokine response (TNF-α) may be of value in clarifying, and ultimately controlling, related host inflammatory responses in septic patients.

Cecal Ligation and Puncture as a Model of Sepsis in the Rat: Influence of the Puncture Size on Mortality, Bacteremia, Endotoxemia and Tumor Necrosis Factor Alpha Levels

2001 ◽  
Vol 33 (2) ◽  
pp. 77-79 ◽  
Author(s):  
E. Otero-Antón ◽  
A. González-Quintela ◽  
A. López-Soto ◽  
S. López-Ben ◽  
J. Llovo ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Cecal Ligation ◽  
Cecal Ligation And Puncture ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Necrosis Factor

scholarly journals Protection against Lipopolysaccharide-Induced Death by Fluoroquinolones

2000 ◽  
Vol 44 (11) ◽  
pp. 3169-3173 ◽  
Author(s):  
Anis A. Khan ◽  
Teri R. Slifer ◽  
Fausto G. Araujo ◽  
Yasuhiro Suzuki ◽  
Jack S. Remington
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Cytokine Production ◽  
Lethal Dose ◽  
Serum Levels ◽  
Protective Effects ◽  
Human Monocytes ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT Because fluoroquinolones have an immunomodulatory effect on cytokine production by lipopolysaccharide (LPS)-treated human monocytes, we examined the effect of fluoroquinolones on the survival of mice injected with a lethal dose of LPS. Trovafloxacin (100 mg/kg), ciprofloxacin (250 mg/kg), and tosufloxacin (100 mg/kg) protected 75% (P = 0.0001), 25% (P = 0.002), and 50% (P = 0.002), respectively, of mice against death. The fluoroquinolones significantly reduced serum levels of interleukin-6 and tumor necrosis factor alpha in LPS-treated mice. The protective effects of fluoroquinolones in LPS-induced shock in mice may also occur in humans.

Serum levels of soluble vascular cell adhesion molecule-1, tumor necrosis factor-α, and interleukin-6 in in vitro fertilization cycles

2009 ◽  
Vol 91 (5) ◽  
pp. 2012-2019 ◽  
Author(s):  
Irene Souter ◽  
Andy Huang ◽  
Otoniel Martinez-Maza ◽  
Elizabeth Crabb Breen ◽  
Alan H. Decherney ◽  
...  
Keyword(s):  
Tumor Necrosis ◽  
Cell Adhesion Molecule ◽  
Tumor Necrosis Factor Α ◽  
Serum Levels ◽  
Vascular Cell Adhesion ◽  
Vitro Fertilization ◽  
Factor Α ◽  
Cell Adhesion Molecule 1 ◽  
Necrosis Factor
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