scholarly journals Tumor Necrosis Factor Alpha Deficiency Improves Endothelial Function and Cardiovascular Injury in Deoxycorticosterone Acetate/Salt-Hypertensive Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-10 ◽  
Author(s):  
Ruiping Cai ◽  
Yun Hao ◽  
Yue-Yang Liu ◽  
Lei Huang ◽  
Yang Yao ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Transforming Growth Factor ◽  
Tap Water ◽  
Renal Diseases ◽  
Control Group ◽  
Deoxycorticosterone Acetate ◽  
Vascular Hypertrophy ◽  
Protein Expressions ◽  
Necrosis Factor

It has been shown that the inflammatory cytokine tumor necrosis factor α (TNFα) plays a role in the development of hypertension and end-stage renal diseases. We hypothesize that TNFα contributes to endothelial dysfunction and cardiac and vascular injury in deoxycorticosterone acetate (DOCA)/salt-hypertensive mice. The wild-type or TNFα-deficient mice were uninephrectomized and implanted with DOCA pellet treatment for 5 weeks; the mice were given either tap water or 1% NaCl drinking water. DOCA mice developed hypertension (systolic blood pressure (SBP): 167±5 vs. 110±4 mmHg in control group, p<0.05), cardiac and vascular hypertrophy, and the impairment of endothelium-dependent relaxation to acetylcholine (EDR). TNFα deficiency improved EDR and lowered cardiac and vascular hypertrophy with a mild reduction in SBP (152±4 vs. 167±5 mmHg in DOCA group, p<0.05) in DOCA mice. The mRNA expressions of the inflammatory cytokines, including TNFα, interleukin 1β (IL1β), monocyte chemotactic protein 1 (MCP1), and monocyte/macrophage marker F4/80 were significantly increased in the aorta of DOCA-hypertensive mice; TNFα deficiency reduced these inflammatory gene expressions. DOCA-hypertensive mice also exhibited an increase in the vascular oxidative fluorescence intensities, the protein expressions of gp91phox and p22phox, and the fibrotic factors transforming growth factor β and fibronectin. TNFα deficiency reduced oxidative stress and fibrotic protein expressions. The DOCA mice also showed a decrease in the protein expression of eNOS associated with increased miR155 expression; TNFα deficiency prevented a decrease in eNOS expression and an increase in miR155 expression in DOCA mice. These results support the idea that TNFα significantly contributes to vascular inflammation, vascular dysfunction, and injury in hypertension.

scholarly journals P0101INHIBITION OF TUMOR NECROSIS FACTOR ALPHA ENHANCED ANTIFIBROTIC EFFECT OF EMPAGLIFLOZIN IN AN ANIMAL MODEL WITH RENAL INSULIN RESISTANCE

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Mohammed Keshawy ◽  
Hoda Mohammed
Keyword(s):  
Insulin Resistance ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Transforming Growth Factor ◽  
Therapeutic Option ◽  
Sirtuin 1 ◽  
Control Group ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Necrosis Factor

Abstract Background and Aims Insulin resistance (IR) has emerged as one of the main risk factors for renal fibrosis (RF) that represents a common stage in almost all chronic kidney disease. The present study aims to investigate the inhibitory effect of empagliflozin (EMPA “a sodium-glucose co-transporter 2 inhibitor”) and infliximab [IFX “a tumor necrosis factor-α (TNF-α) antibody”] on RF in rats with induced IR. Method IR was induced by adding 10% fructose in drinking water for 20 weeks. Thereafter, fructose-induced IR rats were concurrently treated with EMPA (30 mg/kg), IFX (1 dose 5 mg/kg), or EMPA + IFX for 4 weeks, in addition to IR control group (received 10% fructose in water) and normal control (NC) group. Results Rats with IR displayed hyperglycemia, deterioration in kidney functions, glomerulosclerosis, and collagen fiber deposition in renal tissues as compared to NC. This was associated with downregulation of the renal sirtuin 1 (Sirt 1) expression along with higher renal tissue TNF-α and transforming growth factor-β1 (TGF-β1) levels. Both EMPA and IFX significantly modulated the aforementioned fibrotic cytokines, upregulated the renal Sirt 1 expression, and attenuated RF compared to IR control group. Of note, IFX effect was superior to that of EMPA. However, the combination of EMPA and IFX alleviated RF to a greater extent surpassing the monotherapy. This may be attributed to the further upregulation of renal Sirt 1 in addition to the downregulation of fibrotic cytokines. Conclusion These findings suggest that the combination of EMPA and IFX offers additional benefits and may represent a promising therapeutic option for RF.

Exposure to febrile temperature modifies endothelial cell response to tumor necrosis factor-α

2001 ◽  
Vol 90 (1) ◽  
pp. 90-98 ◽  
Author(s):  
Jeffrey D. Hasday ◽  
Douglas Bannerman ◽  
Sirhan Sakarya ◽  
Alan S. Cross ◽  
Ishwar S. Singh ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Gm Csf ◽  
Tnf Α ◽  
Neutrophil Adherence ◽  
Endothelial Cell Response ◽  
Factor Α ◽  
Necrosis Factor

Fever is an important regulator of inflammation that modifies expression and bioactivity of cytokines, including tumor necrosis factor (TNF)-α. Pulmonary vascular endothelium is an important target of TNF-α during the systemic inflammatory response. In this study, we analyzed the effect of a febrile range temperature (39.5°C) on TNF-α-stimulated changes in endothelial barrier function, capacity for neutrophil binding and transendothelial migration (TEM), and cytokine secretion in human pulmonary artery endothelial cells (EC). Permeability for [14C]BSA tracer was increased by treatment with TNF-α, and this effect was augmented by incubating EC at 39.5°C. Treating EC with 2.5 U/ml TNF-α stimulated an increase in subsequent neutrophil adherence and TEM. Incubating EC at 39.5°C caused a 30% increase in TEM but did not modify the enhancement of neutrophil adherence or TEM by TNF-α treatment. Analysis of cytokine expression in EC cultures exposed to TNF-α at either 37° or 39.5°C revealed three patterns of temperature and TNF-α responsiveness. Granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin (IL)-8 were not detectable in untreated EC but were increased after TNF-α exposure, and this increase was enhanced at 39.5°C. IL-6 expression was also increased with TNF-α exposure, but IL-6 expression was lower in 39.5°C EC cultures. Transforming growth factor-β1was constitutively expressed, and its expression was not influenced either by TNF-α or exposure to 39.5°C. These data demonstrate that clinically relevant shifts in body temperature might cause important changes in the effects of proinflammatory cytokines on the endothelium.

Association between tumor necrosis factor-α gene-1031T/C promoter polymorphism and endometriosis in a European population

2019 ◽  
Vol 40 (2) ◽  
Author(s):  
Anastasia Drakou ◽  
Despoina Mavrogianni ◽  
Konstantinos Ntzeros ◽  
Athanasios Protopapas ◽  
Petros Drakakis ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Promoter Polymorphism ◽  
European Population ◽  
Pcr Analysis ◽  
Control Group ◽  
Necrosis Factor Alpha ◽  
Healthy Women ◽  
Tnf Α ◽  
Necrosis Factor

Abstract Background Tumor necrosis factor-alpha (TNF-α) is a pro-inflammatory cytokine which plays an important role in the pathogenesis of many diseases. Endometriosis is one of the most common gynecological diseases. The purpose of this study was to investigate the association of TNF-α-1031T/C polymorphism with the genetic susceptibility of endometriosis in a European population. Materials and methods In this case-control study, 51 endometriosis patients and 67 healthy control women participated. We used endometrial tissue from the patients and peripheral blood from the healthy women to extract DNA. Polymerase chain reaction (PCR) analysis and the restriction enzyme Bbs I were used to analyze the -1031 T/C polymorphism in the TNF-α gene promoter region. Statistical analysis was performed using Fisher’s exact test. We also calculated the odds ratios. Results In the group of patients, 66.7% of women were detected with the TT genotype, 33.3% with the TC genotype and 0% with the CC genotype while in the control group, 46.3% had the TT genotype, 47.8% had the TC genotype and 6% had the CC genotype. There was a significant association between the TT genotype with endometriosis (p = 0.03). There was no significant deviation from the Hardy-Weinberg equilibrium. Conclusions The TC and CC genotypes appeared more often in the healthy women than the endometriosis patients and this shows that the C allele might have a protective role in endometriosis in the Greek population. Further studies are needed to specify the role of this polymorphism in pathogenesis of endometriosis and the mechanisms that protect the patients from the disease.

Importance of Markers of Sepsis in Surgical Patients

2018 ◽  
Vol 84 (6) ◽  
pp. 1058-1063 ◽  
Author(s):  
Marek Smolár ◽  
Ivana Dedinská ◽  
Michal Hošala ◽  
Július Mazúch ◽  
L'Udovit Laca
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Serum Levels ◽  
Control Group ◽  
Risk Of Death ◽  
Significant Difference ◽  
Important Position ◽  
Factor Α ◽  
Necrosis Factor ◽  
Septic Condition

Sepsis, severe sepsis, and septic shock represent a serious medicinal and general social problem and still maintain an important position among the present issues in the basic and clinical research. In the prospective analysis of patients satisfying the criteria of septic condition, we determined serum levels of bioparameters in three consecutive days from the first signs of sepsis depending on the stage or advancement of the septic condition. We determined the most significant parameter/parameters which are able to determine the stage of sepsis or to predict patient's death. In the group of 68 patients, all monitored biomarkers showed significant difference in serum concentrations versus the control group (P = 0.001). The strongest positive connection between the seriousness of sepsis and serum level is in case of procalcitonin. Predictor of mortality (r = -0.468; P = 0.001), transferrin (r = -0.506; P = 0.003), and tumor necrosis factor-α (r = 0.939; P = 0.001). Our results show that the monitored parameters (procalcitonin, C-reactive protein, tumor necrosis factor-a, and interleukin 6) have strong correlations between the serum levels and the stage of disease. Examination of at least one cytokine in normal clinical practice might lead to better interpretation of the patient's condition, determining the risk of death.

Effects of Prostacyclin on Hemodynamics after Intestinal Ischemia-Reperfusion

1997 ◽  
Vol 5 (1) ◽  
pp. 43-47
Author(s):  
S Fehmi Katircioğlu ◽  
Eser Özgencil ◽  
Birol Yamak ◽  
Tulga Ulus ◽  
Selime Ayaz ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Reperfusion Injury ◽  
Tumor Necrosis ◽  
Intestinal Ischemia ◽  
Ischemia Reperfusion ◽  
Venous Pressure ◽  
Control Group ◽  
Central Venous ◽  
Intestinal Ischemia Reperfusion ◽  
Necrosis Factor

Ten rabbits underwent 30 minutes of superior mesenteric artery occlusion to assess the release of tumor necrosis factor, subcellular damage, and hemodynamic changes after intestinal ischemia-reperfusion injury. Five were treated with prostacyclin 5 ng/kg/min 5 minutes before the arterial occlusion. It was increased to 25 ng/kg/min during occlusion, decreased to 5 ng/kg/min for the first 5 minutes of reperfusion, and then discontinued. A control group of 5 rabbits did not receive any pharmacological agent. Specimens were obtained from the small intestine for electron microscopy after 10 minutes and after 60 minutes of reperfusion, while simultaneous blood samples were collected for measurement of tumor necrosis factor. Minimal changes were seen in tissue from the prostacyclin group but severe mitochondrial damage and vacuolation occurred in the control group. The tumor necrosis factor level was 11.97 ± 3.17 U/mL in the control group and 5.06 ± 2.19 U/mL in the prostacyclin group, one hour after the end of mesenteric occlusion ( p < 0.05). Hemodynamic status, assessed by central venous and arterial pressures, was much more affected in the control group than in the prostacyclin group. Mean arterial pressure was 71 ± 5 mm Hg in the control group, and 91 ± 6 mm Hg in the prostacyclin group ( p < 0.05). Central venous pressure was 5.3 ± 0.9 mm Hg in the control group and 2.3 ± 0.7 mm Hg in the prostacyclin group ( p < 0.05). We conclude that intravenous prostacyclin reduced the severity of reperfusion injury occurring during the early period of reperfusion by inhibiting the release of the toxic mediator tumor necrosis factor, thus decreasing distant organ injury.

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