Short-term alpha- or gamma-delta-enriched tocopherol oil supplementation differentially affects the expression of proinflammatory mediators: selective impacts on characteristics of protein tyrosine nitration in vivo

While vitamin E has been used for decades in cattle diets, the principle form used traditionally is the synthetic α-isoform acetate or succinate and largely no data exist on the biological partitioning or functionality of the major naturally occurring γ- and δ-isoforms in cattle. Using tyrosine 3’-nitrated protein (pNT) as a biomarker of nitrosative cell stress, we sought to evaluate the effectiveness of short-term feeding supplementation of high content natural α-tocopherol (α-T, 96% α-isomer) compared to high content γ- and δ-enriched low α-content mixed tocopherol oils (γ-T, ~70% γ-, 20% δ-, <5% α-isoform) to mitigate systemic and hepatic aspects of the proinflammatory response to endotoxin (LPS). Calves fed diets supplemented with α-T, γ-T for five days or no tocopherol supplement (T0E) were challenged with a low-level of LPS (0.25 μg/kg, iv, E. coli 055:B5) sufficient to effect a liver nitration response. As fed, α-T or γ-T increased plasma and liver content of the respective tocopherols reflecting their relative abundance in the respective diets. Plasma or tissue mediators and biomarkers of the proinflammatory response [plasma concentrations of tumor necrosis factor-α (TNF-α, P<0.001), nitrate+nitrite (NOx, P<0.01), and serum amyloid A (SAA, P<0.001)], and general liver content of pNT (P<0.005) increased after LPS. LPS-mediated increases in TNF-α were not dif- ferent between diet treatments; both plasma NOx (P<0.05) and generalized liver pNT (P<0.03) responses were attenuated significantly in α-T and γ-T versus T0E calves. Plasma SAA was significantly decreased in γ-T calves at 24 h post-LPS relative to responses in α-T or T0E calves. The nitration of the mitochondrial proteins 24 h post-LPS was not only attenuated in α-T and γ-T vs T0E, but also the mitigating effect of γ-T on these specific nitration events was greater than that of α-T (P<0.01). Results are consistent with the concept that short-term α-T or γ-T supplementation can effectively decrease proinflammatory liver pNT after LPS; some mitochondrial nitration targets may be better protected with prophylactic supplementation with γ-,δ-tocopherol enriched oil.

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Repetitive Injections of Dendritic Cells Matured with Tumor Necrosis Factor α Induce Antigen-specific Protection of Mice from Autoimmunity

Journal of Experimental Medicine ◽

10.1084/jem.20011341 ◽

2001 ◽

Vol 195 (1) ◽

pp. 15-22 ◽

Cited By ~ 388

Author(s):

Mauritius Menges ◽

Susanne Rößner ◽

Constanze Voigtländer ◽

Heike Schindler ◽

Nicole A. Kukutsch ◽

...

Keyword(s):

T Cells ◽

Dendritic Cells ◽

T Cell ◽

Tumor Necrosis Factor ◽

Tumor Necrosis ◽

Cell Immunity ◽

Tnf Α ◽

Factor Α ◽

Necrosis Factor

Mature dendritic cells (DCs) are believed to induce T cell immunity, whereas immature DCs induce T cell tolerance. Here we describe that injections of DCs matured with tumor necrosis factor (TNF)-α (TNF/DCs) induce antigen-specific protection from experimental autoimmune encephalomyelitis (EAE) in mice. Maturation by TNF-α induced high levels of major histocompatibility complex class II and costimulatory molecules on DCs, but they remained weak producers of proinflammatory cytokines. One injection of such TNF/DCs pulsed with auto-antigenic peptide ameliorated the disease score of EAE. This could not be observed with immature DCs or DCs matured with lipopolysaccharide (LPS) plus anti-CD40. Three consecutive injections of peptide-pulsed TNF/DCs derived from wild-type led to the induction of peptide-specific predominantly interleukin (IL)-10–producing CD4+ T cells and complete protection from EAE. Blocking of IL-10 in vivo could only partially restore the susceptibility to EAE, suggesting an important but not exclusive role of IL-10 for EAE prevention. Notably, the protection was peptide specific, as TNF/DCs pulsed with unrelated peptide could not prevent EAE. In conclusion, this study describes that stimulation by TNF-α results in incompletely matured DCs (semi-mature DCs) which induce peptide-specific IL-10–producing T cells in vivo and prevent EAE.

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Procalcitonin and Proinflammatory Cytokine Clearance during Continuous Venovenous Haemofiltration in Septic Patients

Anaesthesia and Intensive Care ◽

10.1177/0310057x0203000302 ◽

2002 ◽

Vol 30 (3) ◽

pp. 269-274 ◽

Cited By ~ 29

Author(s):

A. A. Dahaba ◽

G. A. Elawady ◽

P. H. Rehak ◽

W. F. List

Keyword(s):

Proinflammatory Cytokine ◽

Tumour Necrosis ◽

Prognostic Markers ◽

Plasma Concentrations ◽

Tumour Necrosis Factor Α ◽

Proinflammatory Mediators ◽

Continuous Venovenous Haemofiltration ◽

The Mean ◽

Factor Α ◽

Necrosis Factor

Procalcitonin (PCT), interleukin-6 (IL-6), tumour necrosis factor α (TNFα), and interleukin-1β (IL-1β) are important clinical prognostic markers in ICU septic patients. The goal of the study was to determine whether continuous venovenous haemofiltration (CVVH), using an AN69 haemofilter, leads to elimination of PCT, TNFα, IL-6 and IL-1βin 13 septic patients with multi-organ failure. At the start of haemofiltration (0), 6 and 12 hours the mean afferent plasma concentration ±SD of PCT (10.1±9.1, 7±6, 5.9±5.7 ng/ml), IL-6 (804.6±847.6, 611.7±528.4, 575.2±539.2 pg/ml), and that of TNFα (4.5±2.6, 4±3.1, 3.8±2.9 pg/ml) significantly declined during CVVH. The efferent plasma concentrations were significantly lower than the corresponding afferent concentrations. PCT, IL-6 and TNFαwere detectable in the ultra-filtrate of all patients. IL-1βwas only detectable in the plasma of eight patients and the ultrafiltrate of five patients. The plasma clearance of PCT, IL-6 and TNFαsignificantly decreased after 12 hours as a result of a decline in the adsorptive elimination of the mediators due to progressive membrane saturation. We demonstrated that if PCT, IL-6 and TNFα are used as clinical prognostic markers in septic patients who are treated with CVVH using an AN69 membrane, one should be aware that their plasma level could be modified by the therapy. In addition CVVH could represent an appropriate tool to remove a broad spectrum of proinflammatory mediators, if such removal is required in septic patients.

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Nonstressed rat model of acute endotoxemia that unmasks the endotoxin-induced TNF-α response

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1999.276.2.h671 ◽

1999 ◽

Vol 276 (2) ◽

pp. H671-H678 ◽

Cited By ~ 3

Author(s):

David W. A. Beno ◽

Robert E. Kimura

Keyword(s):

Rat Model ◽

Endotoxic Shock ◽

Stress Hormones ◽

Tnf Α ◽

Baseline Concentrations ◽

Experimental Protocols ◽

Factor Α ◽

Necrosis Factor

Previous investigators have demonstrated that the tumor necrosis factor-α (TNF-α) response to endotoxin is inhibited by exogenous corticosterone or catecholamines both in vitro and in vivo, whereas others have reported that surgical and nonsurgical stress increase the endogenous concentrations of these stress-induced hormones. We hypothesized that elevated endogenous stress hormones resultant from experimental protocols attenuated the endotoxin-induced TNF-α response. We used a chronically catheterized rat model to demonstrate that the endotoxin-induced TNF-α response is 10- to 50-fold greater in nonstressed (NS) rats compared with either surgical-stressed (SS, laparotomy) or nonsurgical-stressed (NSS, tail vein injection) models. Compared with the NS group, the SS and NSS groups demonstrated significantly lower mean peak TNF-α responses at 2 mg/kg and 6 μg/kg endotoxin [NS 111.8 ± 6.5 ng/ml and 64.3 ± 5.9 ng/ml, respectively, vs. SS 3.9 ± 1.1 ng/ml ( P < 0.01) and 1.3 ± 0.5 ng/ml ( P < 0.01) or NSS 5.2 ± 3.2 ng/ml ( P < 0.01) at 6 μg/kg]. Similarly, baseline concentrations of corticosterone and catecholamines were significantly lower in the NSS group [84.5 ± 16.5 ng/ml and 199.8 ± 26.2 pg/ml, respectively, vs. SS group 257.2 ± 35.7 ng/ml ( P< 0.01) and 467.5 ± 52.2 pg/ml ( P < 0.01) or NS group 168.6 ± 14.4 ng/ml ( P < 0.01) and 1,109.9 ± 140.7 pg/ml ( P < 0.01)]. These findings suggest that the surgical and nonsurgical stress inherent in experimental protocols increases baseline stress hormones, masking the endotoxin-induced TNF-α response. Subsequent studies of endotoxic shock should control for the effects of protocol-induced stress and should measure and report baseline concentrations of corticosterone and catecholamines.

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Analysis of Bone Marrow-derived Mesenchymal Stem Cell Kinetics after Short-term Stimulation with Tumor Necrosis Factor-α (TNF-α)

Journal of Hard Tissue Biology ◽

10.2485/jhtb.28.99 ◽

2019 ◽

Vol 28 (2) ◽

pp. 99-108 ◽

Cited By ~ 1

Author(s):

Mio Naritani ◽

Miho Inoue ◽

Resmi Raju ◽

Mayu Miyagi ◽

Masamitsu Oshima ◽

...

Keyword(s):

Bone Marrow ◽

Stem Cell ◽

Tumor Necrosis Factor ◽

Tumor Necrosis ◽

Tumor Necrosis Factor Α ◽

Cell Kinetics ◽

Short Term ◽

Tnf Α ◽

Factor Α ◽

Necrosis Factor

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Role of interleukin-1 and tumour necrosis factor in leukocyte recruitment to acute dermal inflammation

Mediators of Inflammation ◽

10.1155/s0962935192000528 ◽

1992 ◽

Vol 1 (5) ◽

pp. 347-353 ◽

Cited By ~ 5

Author(s):

Andrew C. Issekutz ◽

Nancy Lopes ◽

Thomas B. Issekutz

Keyword(s):

Monoclonal Antibody ◽

Umbilical Vein ◽

Interleukin 1 ◽

E Coli ◽

Tnf Α ◽

Lps Activation ◽

Necrosis Factor

The cytokines IL-1 and TNF-α are involved in inflammation and their production is stimulated by various agents, especially endotoxin (LPS). Here, using the human IL-1 receptor antagonist (IL-1RA) and a new monoclonal antibody (mAb 7F11) to rabbit TNF, the role of endogenous IL-l and TNF production in acute (3h) leukocyte (PMNL) recruitment to dermal inflammation in rabbits has been studied. IL-1RA inhibited by 27% the PMNL accumulation in reactions induced by killed Escherichia coli (p < 0.05) but not by LPS. The monoclonal antibody to TNF inhibited by 27% and 38% (p < 0.002) the PMNL accumulation in LPS and E. coli reactions respectively, but a combination of the mAb with IL-1RA was not more effective. Treatment of human umbilical vein endothelium with LPS for 3 h activated endothelium to induce PMNL transendothelial migration in vitro, which was not inhibited by IL-1RA, antibody to TNF-α, IL-1 or to IL-8. In conclusion, TNF and IL-1 may partially mediate acute PMNL infiltration in vivo to LPS and Gram negative bacteria, but there is a major IL-1/TNF independent mechanism, at least in dermal inflammation, which may be due to direct LPS activation of the microvasculature or perhaps the generation of cytokines other than IL-1 and TNF.

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MMP-2 Plays an Important Role During the Early Acute Developmental Phase of Oligofructose-Induced Equine Laminitis

Bulletin of the Veterinary Institute in Pulawy ◽

10.1515/bvip-2015-0022 ◽

2015 ◽

Vol 59 (1) ◽

pp. 149-153 ◽

Cited By ~ 1

Author(s):

Xinran Li ◽

Renli Jiang ◽

Guanying Wang ◽

Yue Li ◽

Xiaojing Fan ◽

...

Keyword(s):

P38 Mapk ◽

Plasma Concentrations ◽

Clinical Signs ◽

Tissue Inhibitor Of Metalloproteinase ◽

Matrix Metalloproteinase 2 ◽

Developmental Phase ◽

Tnf Α ◽

Mitogen Activated Protein ◽

Factor Α ◽

Necrosis Factor

Abstract The study was conducted on 24 Mongolian horses, with oligofructose-induced equine laminitis (10 g/kg b.w.). The objective of the study was to investigate the relationships among matrix metalloproteinase 2 (MMP-2), P38 mitogen-activated protein kinases (P38 MAPK), tissue inhibitor of metalloproteinase 2 (TIMP-2), lipopolysaccharides (LPS), and tumour necrosis factor-α (TNF-α) during acute developmental phase of laminitis, and to determine whether there are any characteristic tendencies. Moreover, plasma concentrations of LPS and TNF-α were measured in order to determine the time of leukocytes’ activation. Eleven of the 12 horses showed clinical signs of laminitis. The contents of MMP-2 and P38 MAPK increased significantly from 8 h to 64 h, and the content of TIMP-2 decreased significantly at the same time. Plasma LPS concentrations increased significantly between 8 h and 20 h and reached a peak of 0.024 ± 0.009 EU/mL (equivalent to 3.04 ± 1.19 pg/mL) at 12 h. TNF-α concentration increased between 20 h and 36 h. This data indicates that MMP-2 plays an important role during the early acute developmental phase of oligofructose-induced equine laminitis.

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Combined anticoagulant and antiselectin treatments prevent lethal intravascular coagulation

Blood ◽

10.1182/blood-2001-12-0190 ◽

2003 ◽

Vol 101 (3) ◽

pp. 921-928 ◽

Cited By ~ 28

Author(s):

Keith E. Norman ◽

Matthew J. Cotter ◽

James B. Stewart ◽

Kate B. Abbitt ◽

Majid Ali ◽

...

Keyword(s):

Tumor Necrosis ◽

Tumor Necrosis Factor Α ◽

Platelet Adhesion ◽

Traumatic Shock ◽

Intravascular Coagulation ◽

Tnf Α ◽

Factor Α ◽

Blocking Antibodies ◽

Necrosis Factor

AbstractWidespread microvascular injury followed by vessel obstruction may lead to disseminated intravascular coagulation (DIC). We describe a murine model wherein leukocytes interacting with inflamed microvessels in vivo are activated by antibodies. Treatment of tumor necrosis factor α (TNF-α)–primed mice with anti–Ly-6G antibodies reproduced many of the features of septic or traumatic shock including microvessel obstruction and coagulation, severe vasculitis, respiratory difficulties, and vascular leakage. Mice lacking either E-selectin or P-selectin were protected from this reaction as were animals treated with a combination of either selectin-blocking antibodies and heparin or a selectin antagonist plus heparin. Combined blockade of leukocyte/platelet adhesion and coagulation may provide convincing protection in DIC.

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Adjuvant TNF-α therapy to electrochemotherapy with intravenous cisplatin in murine sarcoma exerts synergistic antitumor effectiveness

Radiology and Oncology ◽

10.1515/raon-2015-0005 ◽

2015 ◽

Vol 49 (1) ◽

pp. 32-40 ◽

Cited By ~ 17

Author(s):

Maja Cemazar ◽

Vesna Todorovic ◽

Janez Scancar ◽

Ursa Lampreht ◽

Monika Stimac ◽

...

Keyword(s):

Tumour Necrosis ◽

Combined Treatment ◽

Growth Delay ◽

Tumour Necrosis Factor Α ◽

Tumour Growth Delay ◽

Tnf Α ◽

Factor Α ◽

Murine Sarcoma ◽

Necrosis Factor

AbstractBackground. Electrochemotherapy is a tumour ablation modality, based on electroporation of the cell membrane, allowing non-permeant anticancer drugs to enter the cell, thus augmenting their cytotoxicity by orders of magnitude. In preclinical studies, bleomycin and cisplatin proved to be the most suitable for clinical use. Intravenous administration of cisplatin for electrochemotherapy is still not widely accepted in the clinics, presumably due to its lower antitumor effectiveness, but adjuvant therapy by immunomodulatory or vascular-targeting agents could provide a way for its potentiation. Hence, the aim of the present study was to explore the possibility of adjuvant tumour necrosis factor α (TNF-α) therapy to potentiate antitumor effectiveness of electrochemotherapy with intravenous cisplatin administration in murine sarcoma.Materials and methods. In vivo study was designed to evaluate the effect of TNF-α applied before or after the electrochemotherapy and to evaluate the effect of adjuvant TNF-α on electrochemotherapy with different cisplatin doses.Results. A synergistic interaction between TNF-α and electrochemotherapy was observed. Administration of TNF-α before the electrochemotherapy resulted in longer tumour growth delay and increased tumour curability, and was significantly more effective than TNF-α administration after the electrochemotherapy. Tumour analysis revealed increased platinum content in tumours, TNF-α induced blood vessel damage and increased tumour necrosis after combination of TNF-α and electrochemotherapy, indicating an anti-vascular action of TNF-α. In addition, immunomodulatory effect might have contributed to curability rate of the tumours.Conclusion. Adjuvant intratumoural TNF-α therapy synergistically contributes to electrochemotherapy with intravenous cisplatin administration. Due to its potentiation at all doses of cisplatin, the combined treatment is predicted to be effective also in tumours, where the drug concentration is suboptimal or in bigger tumours, where electrochemotherapy with intravenous cisplatin is not expected to be sufficiently effective.

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Factors mediating the hemodynamic effects of tumor necrosis factor-α in portal hypertensive rats

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1999.276.3.g687 ◽

1999 ◽

Vol 276 (3) ◽

pp. G687-G693 ◽

Cited By ~ 9

Author(s):

Javier Muñoz ◽

Agustín Albillos ◽

María Pérez-Páramo ◽

Irma Rossi ◽

Melchor Alvarez-Mon

Keyword(s):

Nitric Oxide ◽

Tumor Necrosis ◽

Tumor Necrosis Factor Α ◽

Portal Pressure ◽

Systemic Resistance ◽

Short Term ◽

Tnf Α ◽

Factor Α ◽

Necrosis Factor

Nitric oxide, prostacyclin, and glucagon have been implicated in promoting the hyperdynamic circulatory state of portal hypertension. Recent evidence also indicates that increased tumor necrosis factor-α (TNF-α) production is involved in the pathogenesis of this hemodynamic abnormality. This study was aimed at investigating in rats with portal vein stenosis (PVS) the effects on splanchnic hemodynamics of blocking circulating TNF-α and the factors mediating the vascular action of this cytokine in this setting. Anti-TNF-α polyclonal antibodies or placebo was injected into rats ( n = 96) before and 4 days after PVS (short-term inhibition) and at 24 h and 4, 7, 10 days after PVS (long-term inhibition). Short-term TNF-α inhibition reduced portal venous inflow and cardiac index and increased splanchnic and systemic resistance. Portal pressure was unchanged, but portal-systemic shunting was decreased. After long-term TNF-α inhibition, portal venous inflow and portal pressure were unchanged, but arterial pressure and systemic resistance rose significantly. Anti-TNF-α PVS rats exhibited lower increments of systemic resistance after N ω-nitro-l-arginine methyl ester and indomethacin administration and lower serum levels of TNF-α, nitrates-nitrites, and 6-keto-PGF1α, both over the short and the long term. Serum glucagon levels rose after long-term inhibition. In conclusion, the specific role played by TNF-α in the development of the hyperdynamic state of portal hypertension appears to be mainly mediated through an increased release of nitric oxide and prostacyclin. Maintenance of the splanchnic hyperemia after long-term TNF-α inhibition could be due to a compensatory release of glucagon.

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Effects of Short-Term Exercise Training With and Without Milk Intake on Cardiometabolic and Inflammatory Adaptations in Obese Adolescents

Pediatric Exercise Science ◽

10.1123/pes.2015-0053 ◽

2015 ◽

Vol 27 (4) ◽

pp. 518-524 ◽

Cited By ~ 4

Author(s):

Maple Liu ◽

Linda J. Gillis ◽

Nicholas R. Persadie ◽

Stephanie A. Atkinson ◽

Stuart M. Phillips ◽

...

Keyword(s):

Exercise Intervention ◽

Short Term ◽

Post Exercise ◽

Obese Adolescents ◽

Reactive Protein ◽

Daily Exercise ◽

Tnf Α ◽

Group 3 ◽

Factor Α ◽

Necrosis Factor

There is some evidence that a combination of factors can reduce inflammation and associated metabolic risk factors. We studied the early cardiometabolic and inflammatory adaptations to a short-term exercise intervention with and without milk in obese adolescents. Fifty-four adolescents were randomized to consume milk post exercise (MILK) or a carbohydrate beverage (CONT) during one-week of daily exercise. Insulin levels were not different between the groups post training. Glucose was reduced over time in both groups (-9 ± 13 mg/dl MILK and -6 ± 14 mg/dl CONT, p < .05) but not different between groups. There was a greater decrease in mean arterial pressure (MAP) in the MILK group (-3 ± 6 mmHg MILK vs. 2 ± 7 mmHg CONT, p < .04). Milk provided postexercise did not affect C-reactive protein (CRP), tumor necrosis factor-α (TNF-α) or interleukin-6 (IL-6). The exercise intervention led to an increase in TNF-α in both groups (0.27 ± 0.7 pg/ml MILK and 0.48 ± 0.6 pg/ml CONT, p < .001). The early adaptations to a short-term exercise intervention in obese adolescents include a reduction in MAP and an increase in some inflammatory markers.

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