scholarly journals Coffee Bioactive N-Methylpyridinium Attenuates Tumor Necrosis Factor (TNF)-α-Mediated Insulin Resistance and Inflammation in Human Adipocytes

Biomolecules ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1545
Author(s):  
Stefano Quarta ◽  
Egeria Scoditti ◽  
Maria Annunziata Carluccio ◽  
Nadia Calabriso ◽  
Giuseppe Santarpino ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Pyrolysis Product ◽  
Intercellular Adhesion Molecule ◽  
Peroxisome Proliferator ◽  
Human Adipocytes ◽  
Obesity And Diabetes ◽  
Tnf Α ◽  
Chemokine Ligand ◽  
Necrosis Factor

Although coffee consumption has been historically associated with negative health outcomes, recent evidence suggests a lower risk of metabolic syndrome, obesity and diabetes among regular coffee drinkers. Among the plethora of minor organic compounds assessed as potential mediators of coffee health benefits, trigonelline and its pyrolysis product N-methylpyridinium (NMP) were preliminary shown to promote glucose uptake and exert anti-adipogenic properties. Against this background, we aimed at characterizing the effects of trigonelline and NMP in inflamed and dysfunctional human adipocytes. Human Simpson-Golabi-Behmel syndrome (SGBS) adipocytes were treated with NMP or, for comparison, trigonelline, for 5 h before stimulation with tumor necrosis factor (TNF)-α. NMP at concentrations as low as 1 µmol/L reduced the stimulated expression of several pro-inflammatory mediators, including C-C Motif chemokine ligand (CCL)-2, C-X-C Motif chemokine ligand (CXCL)-10, and intercellular adhesion Molecule (ICAM)-1, but left the induction of prostaglandin G/H synthase (PTGS)2, interleukin (IL)-1β, and colony stimulating factor (CSF)1 unaffected. Furthermore, NMP restored the downregulated expression of adiponectin (ADIPOQ). These effects were functionally associated with downregulation of the adhesion of monocytes to inflamed adipocytes. Under the same conditions, NMP also reversed the TNF-α-mediated suppression of insulin-stimulated Ser473 Akt phosphorylation and attenuated the induction of TNF-α-stimulated lipolysis restoring cell fat content. In an attempt to preliminarily explore the underlying mechanisms of its action, we show that NMP restores the expression of the master regulator of adipocyte differentiation peroxisome proliferator-activated receptor (PPAR)γ and downregulates activation of the pro-inflammatory mitogen-activated protein jun N-terminal kinase (JNK). In conclusion, NMP reduces adipose dysfunction in pro-inflammatory activated adipocytes. These data suggest that bioactive NMP in coffee may improve the inflammatory and dysmetabolic milieu associated with obesity.

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.

Ablation of tumor necrosis factor receptor type I (p55) alters oxygen-induced lung injury

2000 ◽  
Vol 278 (5) ◽  
pp. L1082-L1090 ◽  
Author(s):  
Gloria S. Pryhuber ◽  
David P. O'Brien ◽  
Raymond Baggs ◽  
Richard Phipps ◽  
Heidie Huyck ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Lung Injury ◽  
Tumor Necrosis ◽  
Oxygen Toxicity ◽  
Intercellular Adhesion Molecule ◽  
Type I ◽  
Intratracheal Administration ◽  
Tnf Α ◽  
Early Survival ◽  
Necrosis Factor

Hyperoxic lung injury, believed to be mediated by reactive oxygen species, inflammatory cell activation, and release of cytotoxic cytokines, complicates the care of many critically ill patients. The cytokine tumor necrosis factor (TNF)-α is induced in lungs exposed to high concentrations of oxygen; however, its contribution to hyperoxia-induced lung injury remains unclear. Both TNF-α treatment and blockade with anti-TNF antibodies increased survival in mice exposed to hyperoxia. In the current study, to determine if pulmonary oxygen toxicity is dependent on either of the TNF receptors, type I (TNFR-I) or type II (TNFR-II), TNFR-I or TNFR-II gene-ablated [(−/−)] mice and wild-type control mice (WT; C57BL/6) were studied in >95% oxygen. There was no difference in average length of survival, although early survival was better for TNFR-I(−/−) mice than for either TNFR-II(−/−) or WT mice. At 48 h of hyperoxia, slightly more alveolar septal thickening and peribronchiolar and periarteriolar edema were detected in WT than in TNFR-I(−/−) lungs. By 84 h of oxygen exposure, TNFR-I(−/−) mice demonstrated greater alveolar debris, inflammation, and edema than WT mice. TNFR-I was necessary for induction of cytokine interleukin (IL)-1β, IL-1 receptor antagonist, chemokine macrophage inflammatory protein (MIP)-1β, MIP-2, interferon-γ-induced protein-10 (IP-10), and monocyte chemoattractant protein (MCP)-1 mRNA in response to intratracheal administration of recombinant murine TNF-α. However, IL-1β, IL-6, macrophage migration inhibitory factor, MIP-1α, MIP-2, and MCP-1 mRNAs were comparably induced by hyperoxia in TNFR-I(−/−) and WT lungs. In contrast, mRNA for manganese superoxide dismutase and intercellular adhesion molecule-1 were induced by hyperoxia only in WT mice. Differences in early survival and toxicity suggest that pulmonary oxygen toxicity is in part mediated by TNFR-I. However, induction of specific cytokine and chemokine mRNA and lethality in response to severe hyperoxia was independent of TNFR-I expression. The current study supports the prediction that therapeutic efforts to block TNF-α receptor function will not protect against pulmonary oxygen toxicity.

Association of Genetic Polymorphisms in DC-SIGN, Toll-Like Receptor 3, and Tumor Necrosis Factor α Genes and the Lewis-Negative Phenotype With Chikungunya Infection and Disease in Nicaragua

2020 ◽  
Author(s):  
Filemón Bucardo ◽  
Yaoska Reyes ◽  
Marlen Morales ◽  
Rafaela Briceño ◽  
Fredman González ◽  
...  
Keyword(s):  
Risk Factors ◽  
Tumor Necrosis Factor ◽  
Joint Pain ◽  
Tumor Necrosis ◽  
Intercellular Adhesion Molecule ◽  
Toll Like Receptor ◽  
Odds Ratios ◽  
Tnf Α ◽  
Necrosis Factor ◽  
Negative Phenotype

Abstract Background Chikungunya infections range from subclinical infection to debilitating arthralgia and to chronic inflammatory rheumatism. Tumor necrosis factor (TNF) α, DC-SIGN (dendritic cell–specific intercellular adhesion molecule 3–grabbing nonintegrin), Toll-like receptor (TLR) 3, and blood groups have been directly or indirectly implicated in the susceptibility and pathogenesis of chikungunya. Methods To test the hypothesis that polymorphisms in genes coding for these molecules determine clinical outcomes of chikungunya infection, a retrospective case-control study was performed in León, Nicaragua. The study included 132 case patients and 132 controls, matched for age, sex and neighborhood. Case patients had clinical symptoms of chikungunya, which was diagnosed by means of polymerase chain reaction. Controls were individuals not reporting abrupt presentation of clinical chikungunya-like symptoms. Polymorphisms were identified by TaqMan single-nucleotide polymorphism genotyping assays. Results After adjustment for sociodemographic risk factors, chikungunya disease was associated with polymorphism in DC-SIGN and TLR3 genes (odds ratios, 5.2 and 3.3, respectively), and TNF-α with reduced persistent joint pain (0.24). Persistent joint pain was also associated with age, female sex and other comorbid conditions. Most interestingly, the Lewis-negative phenotype was strongly associated with both symptomatic chikungunya and immunoglobulin G seropositivity (odds ratios, 2.7, and 3.3, respectively). Conclusion This study identified polymorphisms in DC-SIGN, TLR3, and TNF-α genes as well as Lewis-negative phenotype as risk factors for chikungunya infection and disease progression.

scholarly journals Tumor Necrosis Factor (TNF)-α and Interleukin (IL)-1β Down-regulate Intercellular Adhesion Molecule (ICAM)-2 Expression on the Endothelium

1998 ◽  
Vol 6 (5) ◽  
pp. 381-400 ◽  
Author(s):  
Fiona McLaughlin ◽  
Brian P. Hayes ◽  
Carmel M.T. Horgan ◽  
Julian E. Beesley ◽  
Callum J. Campbell ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Adhesion Molecule ◽  
Tumor Necrosis ◽  
Intercellular Adhesion ◽  
Intercellular Adhesion Molecule ◽  
Tnf Α ◽  
Necrosis Factor

scholarly journals Diosgenin, an Activator of 1,25D3-MARRS Receptor/ERp57, Attenuates the Effects of TNF-α by Causing ADAM10-Dependent Ectodomain Shedding of TNF Receptor 1

2017 ◽  
Vol 43 (6) ◽  
pp. 2434-2445 ◽  
Author(s):  
Won Seok Yang ◽  
Soo Young Moon ◽  
Mee Jeong Lee ◽  
Eun Kyoung Lee ◽  
Su-Kil Park
Keyword(s):  
Tumor Necrosis Factor ◽  
Calcium Channel ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Receptor ◽  
Inhibitory Effect ◽  
Intercellular Adhesion Molecule ◽  
Ectodomain Shedding ◽  
Intercellular Adhesion Molecule 1 ◽  
Tnf Α ◽  
Necrosis Factor

Background/Aims: We investigated how diosgenin, a steroidal sapogenin, has anti-tumor necrosis factor-α (TNF-α) effects in human aortic endothelial cells (HAECs). Methods: Tumor necrosis factor receptor 1 (TNFR1) was assessed by Western blot analysis. Intracellular Ca2+ was measured using Fluo-4 AM. Immunofluorescence staining was performed for a disintegrin and metalloprotease 10 (ADAM10). Results: Diosgenin (1 ∼ 100 nM) induced ectodomain shedding of TNFR1 within 30 min and attenuated TNF-α-induced intercellular adhesion molecule-1 (ICAM-1) expression. Upon treatment with diosgenin, extracellular Ca2+ entered into the cells via L-type calcium channels, whereas diosgenin-induced ectodomain shedding of TNFR1 was almost completely inhibited by BAPTA-AM (intracellular Ca2+ chelator), verapamil (L-type calcium channel antagonist) and the absence of extracellular Ca2+. Diosgenin caused translocation of ADAM10 to the cell surface, which was mediated by extracellular Ca2+ influx. Depletion of ADAM10 prevented diosgenin-induced ectodomain shedding of TNFR1 and abolished the inhibitory effect of diosgenin on TNF-α-induced ICAM-1 expression. Diosgenin did not induce extracellular Ca2+ influx and ectodomain shedding of TNFR1 in cells depleted of 1,25D3-membrane associated rapid response steroid-binding receptor (1,25D3-MARRS receptor/ERp57). Conclusion: Diosgenin elicits L-type calcium channel-mediated extracellular Ca2+ influx, and thereby induces ADAM10-mediated ectodomain shedding of TNFR1. This effect of diosgenin was exerted through 1,25D3-MARRS receptor/ERp57.

scholarly journals Tumor Necrosis Factor Alpha: Role in the Development of Obesity and Diabetes Mellitus

2020 ◽  
pp. 29-42
Author(s):  
Zulaykho M. Shamansurova ◽  
Talat S. Saatov ◽  
Lola Sh. Takhirov
Keyword(s):  
Diabetes Mellitus ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
World Health ◽  
Necrosis Factor Alpha ◽  
Obesity And Diabetes ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

Obesity and Diabetes Mellitus (DM) are defined as worldwide pandemics by the World health organization due to their economic burden and widespread. Although a huge amount of research is being done in the field of obesity and DM today, many questions remain unsolved. Tissue inflammation is the main factor in the development of both obesity and DM, leading towards irreversible changes in the tissue and formation of specific complications. One of the widespread cytokines, tumor necrosis factor alpha (TNF-α), was shown to be involved with inflammation in the development of metabolic disorders and neurodegenerative diseases. Even though the role of TNF-α in the pathogenesis of these two diseases remains unclear, new ways of treating and preventing diseases based on TNF-α antagonism attracted the attention of scientists. In this review, TNF-α and its receptors’ structures and properties are explored, and their role in disease development, including obesity and type 2 DM (DM2) will be discussed by viewing data from literature.

#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 Association of tumor necrosis factor-alpha -308 G/A and -238 G/A polymorphism with diabetic retinopathy: a systematic review and updated meta-analysis.

2020 ◽  
Author(s):  
Wenna Gao ◽  
Ruilin Zhu ◽  
liu yang
Keyword(s):  
Diabetic Retinopathy ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Meta Analysis ◽  
Entire Group ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

Background: Mounting evidence has suggested tumor necrosis factor-alpha (TNF-α) can promote the development of diabetic retinopathy (DR), and TNF-α gene variants may influence DR risk. However, the results are quite different. Objectives: To comprehensively address this issue, we performed the meta-analysis to evaluate the association of TNF-α-308 G/A and -238 G/A polymorphism with DR. Method: Data were retrieved in a systematic manner and analyzed using STATA Statistical Software. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations. Allelic and genotypic comparisons between cases and controls were evaluated. Results: For the TNF-α-308 G/A polymorphism, overall analysis suggested a marginal association with DR [the OR(95%CI) of (GA versus GG), (GA + AA) versus GG, and (A versus G) are 1.21(1.04, 1.41), 1.20(1.03, 1.39), and 1.14(1.01, 1.30), respectively]. And the subgroup analysis indicated an enhanced association among the European population. For the TNF-α-238 G/A polymorphism, there was mild correlation in the entire group [the OR(95%CI) of (GA versus GG) is 1.55(1.14,2.11) ], which was strengthened among the Asian population. Conclusion: The meta-analysis suggested that -308 A and -238 A allele in TNF-α gene potentially increased DR risk and showed a discrepancy in different ethnicities.

Sign in / Sign up

Export Citation Format

Share Document