scholarly journals Tumor necrosis factor-α/interleukin-10 balance in normal and cystic fibrosis children

2001 ◽  
Vol 10 (4) ◽  
pp. 191-197 ◽  
Author(s):  
Galina V. Shmarina ◽  
Alexander L. Pukhalsky ◽  
Svetlana N. Kokarovtseva ◽  
Daria A. Pukhalskaya ◽  
Lidia A. Shabalova ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Interleukin 10 ◽  
Healthy Children ◽  
Linear Association ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Background:The balance between tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) is important for immune homeostasis maintenance. Exuberant production of TNF-α contributes to overwhelming inflammatory response and tissue damage. But, commonly, increase in TNF-α is counterbalanced by simultaneous synthesis of an anti-inflammatory cytokine IL-10, which suppresses production of many activating and regulatory mediators.Aims:In the present study, the relationships between TNF-α and IL-10 in the plasma of healthy schoolchildren and cystic fibrosis (CF) patients have been investigated.Methods:Blood samples were obtained from 12 CF patients with chronic pulmonary disease and 18 healthy schoolchildren vaccinated with live attenuated rubella vaccine. IL-10 and TNF-α were determined in the plasma samples using commercially available enzyme-linked immunosorbent assay kits.Results:Before vaccination, most healthy children (13 of 18) demonstrated superiority of pro-inflammatory TNF-α over anti-inflammatory IL-10 (TNF-α/IL-10 Â 1). In these subjects, a significant positive linear association between the cytokine values has been found. Vaccine challenge resulted in a marked reduction of TNF-α/IL-10 ratios. In addition, a disappearance of correlation between the cytokine values was observed. Such disturbance was related to exuberant elevation of the IL-10 levels after inoculation. On the contrary, in CF individuals, plasma cytokine values remained in strong linear association independently of TNF-α or IL-10 predominance. No spikes in the plasma levels of IL-10 in CF patients during a 6-month observation period have been revealed.Conclusions:There were no fundamental differences between CF and healthy children in the regulation of TNF-α and IL-10 secretion. Thus, immune quiescence seemed to be associated with the predominance of TNF-α, whereas immune disturbance was characterized by IL-10 superiority. The only abnormality that was found in CF patients consisted of their inability to produce unlimitedly IL-10 in response to antigen stimuli.

Increased elastase release by CF neutrophils is mediated by tumor necrosis factor-α and interleukin-8

2000 ◽  
Vol 278 (1) ◽  
pp. L33-L41 ◽  
Author(s):  
Clifford Taggart ◽  
Raymond J. Coakley ◽  
Peter Greally ◽  
Gerry Canny ◽  
Shane J. O'Neill ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Cystic Fibrosis ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Normal Subjects ◽  
Tnf Α ◽  
Blood Neutrophils ◽  
Factor Α ◽  
Necrosis Factor

Cystic fibrosis (CF) is a lethal, hereditary disorder characterized by a neutrophil-dominated inflammation of the lung. We sought to determine whether neutrophils from individuals with CF release more neutrophil elastase (NE) than neutrophils from normal subjects. Our results showed that peripheral blood neutrophils (PBNs) from normal subjects and individuals with CF contained similar amounts of NE, but after preincubation with CF bronchoalveolar lavage (BAL) fluid, significantly more NE was released by CF PBNs, a release that was amplified further by incubation with opsonized Escherichia coli. To determine which components of CF BAL fluid stimulated this excessive NE release from CF PBNs, we repeated the experiments after neutralization or immunoprecipitation of tumor necrosis factor (TNF)-α and interleukin (IL)-8 in CF BAL fluid. We found that subsequent NE release from CF PBNs was reduced significantly when TNF-α and IL-8 were removed from CF BAL fluid. When TNF-α and IL-8 were used as activating stimuli, CF PBNs released significantly greater amounts of NE compared with PBNs from control subjects and individuals with bronchiectasis. These results indicate that CF PBNs respond abnormally to TNF-α and IL-8 in CF BAL fluid and react to opsonized bacteria by releasing more NE. This may help explain the increased NE burden seen in this condition.

Interleukin 10 and Tumor Necrosis Factor-α Genotypes in Rheumatoid Arthritis — Association with Clinical Response to Glucocorticoids

2010 ◽  
Vol 37 (3) ◽  
pp. 503-511 ◽  
Author(s):  
BANESA de PAZ ◽  
MERCEDES ALPERI-LÓPEZ ◽  
FRANCISCO J. BALLINA-GARCÍA ◽  
CATUXA PRADO ◽  
LOURDES MOZO ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Tumor Necrosis Factor ◽  
Clinical Response ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Interleukin 10 ◽  
Functional Polymorphisms ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Objective.There are dysregulated levels of interleukin 10 (IL-10) and tumor necrosis factor-α (TNF-α) in rheumatoid arthritis (RA), and their role in the disease is controversial. We analyzed the association of functional polymorphisms of IL-10 and TNF-α with susceptibility and disease characteristics at the time of diagnosis, and we also evaluated their possible use as predictors of clinical response to treatments.Methods.Patients with recent-onset RA (n = 162) and healthy controls (n = 373) were genotyped for −1082 IL-10 and −308 TNF-α polymorphisms and data were related to clinical and immunological measurements of patients at the time of diagnosis. Response to treatment after 6 months was determined in 125 patients by the absolute change in Disease Activity Score (DAS28) and the American College of Rheumatology criteria for improvement.Results.We found a reduced frequency of the low IL-10 producer genotype (−1082AA) in patients with RA compared to controls (26.5% vs 38.9%; p = 0.006), while it is a risk factor for anticyclic citrullinated peptide antibodies (anti-CCP) positivity (p = 0.028). Evaluation of clinical response to treatments indicated that carriage of the high IL-10 genotype was associated with a favorable outcome (p = 0.009), specifically to prednisone therapy (p = 0.0003). No significant effects were observed with TNF-α polymorphism alone; however, in combination with the IL-10 genotype, it increased the strength of these associations.Conclusion.Results show an association between the low IL-10 producer genotype and protection from RA; nevertheless, when other specific genetic and/or environmental factors trigger onset of RA, this genotype may predispose to development of anti-CCP+ RA disease with reduced response to prednisone treatment.

#50 Gestational exposure of tumor necrosis factor-α (TNF-α) inhibitor drugs

2019 ◽  
Vol 88 ◽  
pp. 149-150 ◽  
Author(s):  
Erkoseoglu Ilknur ◽  
Kadioglu Mine ◽  
Cavusoglu Irem ◽  
Sisman Mulkiye ◽  
Aran Turhan ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Gestational Exposure ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

scholarly journals Tumor necrosis factor α Inhibition for Alzheimer’s Disease

2017 ◽  
Vol 9 ◽  
pp. 117957351770927 ◽  
Author(s):  
Rudy Chang ◽  
Kei-Lwun Yee ◽  
Rachita K Sumbria
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Short Review ◽  
Tnf Α ◽  
Factor Α ◽  
Ad Therapy ◽  
Necrosis Factor

Tumor necrosis factor α (TNF-α) plays a central role in the pathophysiology of Alzheimer’s disease (AD). Food and Drug Administration–approved biologic TNF-α inhibitors are thus a potential treatment for AD, but they do not cross the blood-brain barrier. In this short review, we discuss the involvement of TNF-α in AD, challenges associated with the development of existing biologic TNF-α inhibitors for AD, and potential therapeutic strategies for targeting TNF-α for AD therapy.

Tumor necrosis factor-α-associated lysosomal permeabilization is cathepsin B dependent

2002 ◽  
Vol 283 (4) ◽  
pp. G947-G956 ◽  
Author(s):  
Nathan W. Werneburg ◽  
M. Eugenia Guicciardi ◽  
Steven F. Bronk ◽  
Gregory J. Gores
Keyword(s):  
Tumor Necrosis Factor ◽  
Cathepsin B ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Fluorescent Protein ◽  
Tnf Α ◽  
Calcein Release ◽  
Green Fluorescent ◽  
Factor Α ◽  
Necrosis Factor

Cathepsin B (Cat B) is released from lysososomes during tumor necrosis factor-α (TNF-α) cytotoxic signaling in hepatocytes and contributes to cell death. Sphingosine has recently been implicated in lysosomal permeabilization and is increased in the liver by TNF-α. Thus the aims of this study were to examine the mechanisms involved in TNF-α-associated lysosomal permeabilization, especially the role of sphingosine. Confocal microscopy demonstrated Cat B-green fluorescent protein and LysoTracker Red were both released from lysosomes after treatment of McNtcp.24 cells with TNF-α/actinomycin D, a finding compatible with lysosomal destabilization. In contrast, endosomes labeled with Texas Red dextran remained intact, suggesting lysosomes were specifically targeted for permeabilization. LysoTracker Red was released from lysosomes in hepatocytes treated with TNF-α or sphingosine in Cat B(+/+) but not Cat B(−/−) hepatocytes, as assessed by a fluorescence-based assay. With the use of a calcein release assay in isolated lysosomes, sphingosine permeabilized liver lysosomes isolated from Cat B(+/+) but not Cat B(−/−) liver. C6ceramide did not permeabilize lysosomes. In conclusion, these data implicate a sphingosine-Cat B interaction inducing lysosomal destabilization during TNF-α cytotoxic signaling.

Tumor Necrosis Factor-α −308 Genotypes Influence Inflammatory Activity and TNF-α Serum Concentrations in Children with Juvenile Idiopathic Arthritis

2009 ◽  
Vol 36 (4) ◽  
pp. 837-842 ◽  
Author(s):  
ANA FILIPA MOURÃO ◽  
JOANA CAETANO-LOPES ◽  
PAULA COSTA ◽  
HELENA CANHÃO ◽  
MARIA JOSÉ SANTOS ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Tumor Necrosis Factor ◽  
Disease Activity ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Inflammatory Activity ◽  
Serum Concentrations ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Objective.Considering the relevance of tumor necrosis factor-α (TNF-α) in the pathophysiology of juvenile idiopathic arthritis (JIA), it is likely that polymorphisms in its promoter area may be relevant in disease susceptibility and activity. We investigated if clinical measures of JIA activity and TNF-α serum concentrations were associated with TNF-α −308 genotypes.Methods.Portuguese patients with JIA in 5 pediatric rheumatology centers were recruited consecutively, along with a control group of healthy subjects. Demographic and clinical data and blood samples were collected from each patient. DNA was extracted for analysis of TNF-α gene promoter polymorphisms at position −308 by restriction fragment-length polymorphism.Results.One hundred fourteen patients and 117 controls were evaluated; 57% of patients presented the oligoarticular subtype, 25% the polyarticular subtype, 8% the systemic subtype, and 9% had enthesitis-related arthritis and 5% psoriatic arthritis. Twenty-four percent of the patients presented the −308 GA/AA genotypes and 76% the −308 GG genotype, similar to findings in controls. Patients with the −308 GA/AA genotype had higher degree of functional impairment, erythrocyte sedimentation rate, 100-mm visual analog scale score for disease activity, and TNF-α levels compared to those with the −308 GG genotype.Conclusion.TNF-α −308 GA/AA genotypes were found to be related to higher inflammatory activity and worse measures of disease activity in Portuguese patients with JIA. They were not associated with susceptibility to JIA.

scholarly journals Tumor Necrosis Factor α Regulates Responses to Nerve Growth Factor, Promoting Neural Cell Survival but Suppressing Differentiation of Neuroblastoma Cells

2008 ◽  
Vol 19 (3) ◽  
pp. 855-864 ◽  
Author(s):  
Yoshinori Takei ◽  
Ronald Laskey
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Neuroblastoma Cells ◽  
Erk Activation ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Although nerve growth factor (NGF) promotes survival of neurons, tumor necrosis factor α (TNF-α) contributes to cell death triggered by NGF depletion, through TNF-α receptor (TNFR) 1. In contrast to this effect, TNF-α can promote neural cell survival via TNF-α receptor TNFR2. Although these findings demonstrate pivotal roles of TNF-α and NGF in cell fate decisions, cross-talk between these signaling pathways has not been clarified. We find that NGF can induce TNF-α synthesis through the nuclear factor-κB transcription factor. This provides a new basis for examining the cross-talk between NGF and TNF-α. Inhibition of TNFR2 shows opposite effects on two downstream kinases of NGF, extracellular signal-regulated kinase (Erk) and Akt. It increases Erk activation by NGF, and this increased activation induces differentiation of neuroblastoma cell lines. Reciprocally, inhibition of TNFR2 decreases Akt activation by NGF. Consistent with an essential role of Akt in survival signaling, inhibition of TNF-α signaling decreases NGF-dependent survival of neurons from rat dorsal root ganglia. Thus, NGF and NGF-induced TNF-α cooperate to activate Akt, promoting survival of normal neural cells. However, the NGF-induced TNF-α suppresses Erk activation by NGF, blocking NGF-induced differentiation of neuroblastoma cells. TNFR2 signaling could be a novel target to modulate cell responses to NGF.

Interleukin-1 and tumor necrosis factor-α increase insulin-like growth factor-binding protein-3 (IGFBP-3) production and IGFBP-3 protease activity in human articular chondrocytes

1995 ◽  
Vol 146 (2) ◽  
pp. 279-286 ◽  
Author(s):  
R C Olney ◽  
D M Wilson ◽  
M Mohtai ◽  
P J Fielder ◽  
R L Smith
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Articular Chondrocytes ◽  
Tnf Α ◽  
Igf I ◽  
Matrix Production ◽  
Factor Α ◽  
Necrosis Factor ◽  
Igfbp 3

Abstract IGF-I is the major anabolic factor for cartilage matrix production. Chondrocytes and cartilage treated with interleukin-1α (IL-1α), and chondrocytes from several models of inflammatory joint disease, exhibit reduced responsiveness to IGF-I. Since the IGF-binding proteins (IGFBPs) modulate the effects of IGF-I, we examined the effect of IL-1α and tumor necrosis factor-α (TNF-α) on IGFBP production by normal human articular chondrocytes in primary culture. Western ligand blots and immunoprecipitation of conditioned medium samples showed that articular chondrocytes produced IGFBPs-2, −3 and −4 and glycosylated IGFBP-4. Both IL-1α and TNF-α increased chondrocyte production of IGFBP-3, but did not alter IGFBP-4 production. The activity of a neutral metalloprotease with the ability to cleave IGFBP-3 was also increased by IL-1α. These data suggest that the cytokines IL-1α and TNF-α may act to reduce IGF-I access to chondrocytes by increasing production of IGFBP-3. This may be a factor in the decreased matrix production in the inflammatory arthritides. Journal of Endocrinology (1995) 146, 279–286

scholarly journals Targeted Deletion of Class A Macrophage Scavenger Receptor Increases the Risk of Cardiac Rupture After Experimental Myocardial Infarction

Circulation ◽  
2007 ◽  
Vol 115 (14) ◽  
pp. 1904-1911 ◽  
Author(s):  
Kenichi Tsujita ◽  
Koichi Kaikita ◽  
Takanori Hayasaki ◽  
Tsuyoshi Honda ◽  
Hironori Kobayashi ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Interleukin 10 ◽  
Experimental Myocardial Infarction ◽  
Cardiac Rupture ◽  
Infarcted Myocardium ◽  
Factor Α ◽  
Necrosis Factor

Background— Class A macrophage scavenger receptor (SR-A) is a macrophage-restricted multifunctional molecule that optimizes the inflammatory response by modulation of the activity of inflammatory cytokines. This study was conducted with SR-A–deficient (SR-A −/− ) mice to evaluate the relationship between SR-A and cardiac remodeling after myocardial infarction. Methods and Results— Experimental myocardial infarction (MI) was produced by ligation of the left coronary artery in SR-A −/− and wild-type (WT) male mice. The number of mice that died within 4 weeks after MI was significantly greater in SR-A −/− mice than in WT mice ( P =0.03). Importantly, death caused by cardiac rupture within 1 week after MI was 31% (17 of 54 mice) in SR-A −/− mice and 12% (6 of 51 mice) in WT mice ( P =0.01). In situ zymography demonstrated augmented gelatinolytic activity in the infarcted myocardium in SR-A −/− mice compared with WT mice. Real-time reverse transcription–polymerase chain reaction at day 3 after MI showed that the expression of matrix metalloproteinase-9 mRNA increased significantly in the infarcted myocardium in SR-A −/− mice compared with WT mice. Furthermore, SR-A −/− mice showed augmented expression of tumor necrosis factor-α and reduction of interleukin-10 in the infarcted myocardium at day 3 after MI. In vitro experiments also demonstrated increased tumor necrosis factor-α and decreased interleukin-10 expression in activated SR-A −/− macrophages. Conclusions— The present findings suggest that SR-A deficiency might cause impairment of infarct remodeling that results in cardiac rupture via insufficient production of interleukin-10 and enhanced expression of tumor necrosis factor-α and of matrix metalloproteinase-9. SR-A might contribute to the prevention of cardiac rupture after MI.

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