scholarly journals FEATURES OF THE IMMUNE RESPONSE FORMATION TO THERMAL TRAUMA

2021 ◽  
Vol 67 (6) ◽  
pp. 32-39
Author(s):  
O.M. Lynnyk ◽  
◽  
O.I. Osadcha ◽  
H.P. Kozynets ◽  
I.R. Yanchiy ◽  
...  
Keyword(s):  
Immune Response ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Burn Injury ◽  
Neutrophilic Granulocytes ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Factor Α ◽  
Necrosis Factor

To study the effect of thermal trauma on the immune response formation, 43 patients aged 16 to 58 with body surface area of burns 20-60% were examined. The neutrophilic granulocytes (NG) and monocytes functional activity, the content of myeloperoxidase and substances with a positive reaction to Schiff’s periodic acid (PAS- stained substances), the cytokines content were determined: interleukin-1β (IL-1β), IL-2, IL-4, IL- 6, tumor necrosis factor-α (TNF-α). Thermal damage caused changes in the immune response, which were characterized by a pro-inflammatory phase in which innate immunity cells (neutrophilic granulocytes, monocytes) acquired high functional activity, producing a higher content of proinflammatory cytokines. On the 2-3rd day after the burn injury in the peripheral blood, the interleukin-1β (IL-1β) content was 133.5 ± 21.1 pg/ml, the tumor necrosis factor α (TNF-α) content was 265 ± 115.5 pg/ml, which exceeded the reference values by 5.1 and 10.9 times, respectively. The content of IL-6 on the 2-3rd day was 85.30 ± 13.10 pg/ml. Also a concomitant syndrome of compensatory anti-inflammatory response developed with increasing production of anti-inflammatory IL-4: on the 2-3rd day after burn injury, its content was 268.5 pg/ml, exceeding the reference values by 8.2 times. The content of anti-inflammatory IL-10 was decreased. This suggests that anti-inflammatory cytokines do not compensate for the high content of pro-inflammatory factors. On the 7th-8th day after the burn injury, there was a tendency to further increase the content of pro-inflammatory cytokines IL- 1β and TNF-α to 148.0 ± 27.0, and 281.2 ± 146.7 pg/ml, respectively, while the content of IL-6 on the 7-8th day was 131.0 ± 11.1 pg/ml, the anti-inflammatory cytokine IL-10 increased slightly, and the content of IL-4 decreased. These changes in the early period of burn disease dynamics, as well as reduced activity of myeloperoxidase and PAS- stained substances NG, point for a functional deficiency of NG, reduced enzymatic activity and cells energy resources decompensation. These changes could clinically lead to SIRS progression and multiorgan dysfunction.

scholarly journals Modification of Tumor Necrosis Factor-α and C-C Motif Chemokine Ligand 18 Secretion by Monocytes Derived from Patients with Diabetic Foot Syndrome

Biology ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 3
Author(s):  
Karine O. Galstyan ◽  
Ludmila V. Nedosugova ◽  
Narine S. Martirosian ◽  
Nikita G. Nikiforov ◽  
Natalia V. Elizova ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Diabetic Foot ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Tnf Α ◽  
Inflammatory Activation ◽  
Chemokine Ligand ◽  
Anti Inflammatory ◽  
Factor Α ◽  
Necrosis Factor

Background: This study involves the investigation of spontaneous and induced secretion of the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) and the anti-inflammatory chemokine C-C motif chemokine ligand 18 (CCL18) by monocytes isolated from blood of patients with long-term type 2 diabetes mellitus (T2DM), both with or without foot ulcers. Methods: A total of 121 patients with T2DM (79 without diabetic foot syndrome (DFS) and 42 patients with DFS) were included. Cluster of Differentiation 14 (CD14+) monocytes were isolated from patients’ blood and stimulated by interferon-γ (IFN-γ) and interleukin-4 (IL-4) for induction of pro- and anti-inflammatory monocyte activation, respectively. The concentrations of TNF-α and CCL18 in the culture medium were measured using ELISA on day 1 and day 6 after cell stimulation. Results: We found a correlation between glycated hemoglobin (HbA1c) and stimulated secretion levels of TNF-α (r = 0.726, p = 0.027) and CCL18 (r = –0.949, p = 0.051) in patients with DFS. There was an increase of pro- and anti-inflammatory activation of monocytes in all patients with different durations of DFS (p < 0.05). However, no stimulation of anti-inflammatory activation was detected in patients with DFS lasting more than 6 months (p = 0.033). Conclusions: Our study showed an increase in pro-inflammatory secretion and a decrease in anti-inflammatory secretion by monocytes isolated from blood of patients with T2DM depending on HbA1c levels and duration of the inflammatory process. These findings allow us to assume that monocytes isolated from T2DM patients are characterized by a biased ability to respond towards pro-inflammatory stimulation, contributing to the chronic wound process.

scholarly journals Fatsia polycarpa Triterpenoids and Acetylated Derivatives Thereof Inhibit Tumor Necrosis Factor-α-Induced Inflammation

2017 ◽  
Vol 12 (9) ◽  
pp. 1934578X1701200
Author(s):  
Chang-Hung Chou ◽  
Yan-Ting Lu ◽  
Shi-Yie Cheng ◽  
Hsueh-Ling Cheng
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Raw 264.7 Cells ◽  
Induced Expression ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Factor Α ◽  
Necrosis Factor

Fatsia polycarpa Hayata is an evergreen shrub endemic to Taiwan and used locally to treat several inflammatory disorders. The crude extract of F. polycarpa has been proven to exhibit an anti-inflammatory effect in vitro and in vivo; however, which constituents of the extract confer the anti-inflammatory function remains unclear. Fatsicarpain D (Fat D) and fatsicarpain F (Fat F) are oleanane-type triterpenoids and two of the feature constituents of the F polycarpa extract. Ester substitution on C-3 has been proposed to enhance the activities of triterpenoids. Thus, this study compared and characterized the anti-inflammatory activities of Fat D, Fat F, and the C-3-acetylated derivatives thereof. These compounds were toxic to RAW 264.7 cells, but not to FL83B cells. The compounds dose-dependently inhibited tumor necrosis factor-α (TNF-α)-induced expression of inducible nitric oxide synthase in FL83B cells, with the IC50 values being Fat D 8.5 μM, acetylated Fat D 10.4 μM, acetylated Fat F 10.7 μM, and Fat F 27.4 μM, respectively. Thus, acetylation of C-3 improved the activity of Fat F. Moreover, the compounds suppressed TNF-α-induced expression of nuclear factor-κB (NF-κB) p65 subunit and protein tyrosine phosphatase-1B. Furthermore, they inhibited TNF-α-mediated activation of the inhibitor kappa B kinase (IKK), and that of the mitogen-activated protein kinases (MAPKs) extracellular-signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK), but promoted the activation of MAPK p38, which was found to be anti-inflammatory in certain cell types. Thus, Fat D and Fat F exhibited obvious anti-inflammatory activities in vitro and inhibited ERK, JNK, and the IKK/NF-κB pathway.

#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.

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