scholarly journals Berry Phenolic and Volatile Extracts Inhibit Pro-Inflammatory Cytokine Secretion in LPS-Stimulated RAW264.7 Cells through Suppression of NF-κB Signaling Pathway

Antioxidants ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 871
Author(s):  
Inah Gu ◽  
Cindi Brownmiller ◽  
Nathan B. Stebbins ◽  
Andy Mauromoustakos ◽  
Luke Howard ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Nuclear Translocation ◽  
Complex Mixture ◽  
Limited Information ◽  
Potential Health ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Factor Α ◽  
Raw264.7 Macrophage ◽  
Necrosis Factor

Berries are a rich source of phytochemicals, especially phenolics well known for protective activity against many chronic diseases. Berries also contain a complex mixture of volatile compounds that are responsible for the unique aromas of berries. However, there is very limited information on the composition and potential health benefits of berry volatiles. In this study, we isolated phenolic and volatile fractions from six common berries and characterized them by HPLC/HPLC-MS and GC/GC-MS, respectively. Berry phenolic and volatile fractions were evaluated for an anti-inflammatory effect using lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells by measuring levels of pro-inflammatory cytokines and the nuclear factor-kappa B (NF-κB) signaling pathway. Results showed that LPS-induced excessive production of nitric oxide (NO), prostaglandin E2 (PGE2), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), which were inhibited by berry phenolic and volatile extracts. Moreover, berry phenolic and volatile extracts reduced the nuclear translocation of NF-κB by blocking the phosphorylation of p65 and degradation of IκBα. These findings showed that berry volatiles from six berries had comparable anti-inflammatory effects to berry phenolics through the suppression of pro-inflammatory mediators and cytokines expression via NF-κB down-regulation, despite being present in the fruit at a lower concentration.

scholarly journals Anti-Inflammatory Effect of Simonsinol on Lipopolysaccharide Stimulated RAW264.7 Cells through Inactivation of NF-κB Signaling Pathway

Molecules ◽  
2020 ◽  
Vol 25 (16) ◽  
pp. 3573
Author(s):  
Lian-Chun Li ◽  
Zheng-Hong Pan ◽  
De-Sheng Ning ◽  
Yu-Xia Fu
Keyword(s):  
Nitric Oxide ◽  
Signaling Pathway ◽  
Morphological Changes ◽  
Raw264.7 Cells ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Factor Α ◽  
Oxide Synthase ◽  
Necrosis Factor

Simonsinol is a natural sesqui-neolignan firstly isolated from the bark of Illicium simonsii. In this study, the anti-inflammatory activity of simonsinol was investigated with a lipopolysaccharide (LPS)-stimulated murine macrophages RAW264.7 cells model. The results demonstrated that simonsinol could antagonize the effect of LPS on morphological changes of RAW264.7 cells, and decrease the production of nitric oxide (NO), tumor necrosis factor α (TNF-α), and interleukin 6 (IL-6) in LPS-stimulated RAW264.7 cells, as determined by Griess assay and enzyme-linked immunosorbent assay (ELISA). Furthermore, simonsinol could downregulate transcription of inducible nitric oxide synthase (iNOS), TNF-α, and IL-6 as measured by reverse transcription polymerase chain reaction (RT-PCR), and inhibit phosphorylation of the alpha inhibitor of NF-κB (IκBα) as assayed by Western blot. In conclusion, these data demonstrate that simonsinol could inhibit inflammation response in LPS-stimulated RAW264.7 cells through the inactivation of the nuclear transcription factor kappa-B (NF-κB) signaling pathway.

scholarly journals Essential Oil of Myrtus communis Inhibits Inflammation in Rats by Reducing Serum IL-6 and TNF-α

2011 ◽  
Vol 6 (10) ◽  
pp. 1934578X1100601 ◽  
Author(s):  
Andrea Maxia ◽  
Maria Assunta Frau ◽  
Danilo Falconieri ◽  
Manvendra Singh Karchuli ◽  
Sanjay Kasture
Keyword(s):  
Essential Oil ◽  
Inflammatory Activity ◽  
Myrtus Communis ◽  
Ear Edema ◽  
Tnf Α ◽  
Cotton Pellet ◽  
Anti Inflammatory ◽  
Factor Α ◽  
Necrosis Factor ◽  
Serum Tumor Necrosis

The topical anti-inflammatory activity of the essential oil of Myrtus communis L. was studied using croton oil induced ear edema and myeloperoxidase (MPO) activity in mice, and cotton pellet induced granuloma, and serum tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in rats. On topical application, the oil exhibited a significant decrease in the ear edema as well as MPO activity. The oil also inhibited cotton pellet-induced granuloma and serum TNF-α and IL-6. It can be concluded that the essential oil of Myrtus communis reduces leukocyte migration to the damaged tissue and exhibits anti-inflammatory activity.

scholarly journals A mechanism of suppression of TGF–β/SMAD signaling by NF-κB/RelA

2000 ◽  
Vol 14 (2) ◽  
pp. 187-197 ◽  
Author(s):  
Markus Bitzer ◽  
Gero von Gersdorff ◽  
Dan Liang ◽  
Alfredo Dominguez-Rosales ◽  
Amer A. Beg ◽  
...  
Keyword(s):  
Transforming Growth Factor ◽  
Nuclear Translocation ◽  
Transforming Growth Factor Β ◽  
Nuclear Factor Κb ◽  
Transcriptional Responses ◽  
Smad Signaling ◽  
Antisense Mrna ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

A number of pathogenic and proinflammatory stimuli, and the transforming growth factor-β (TGF-β) exert opposing activities in cellular and immune responses. Here we show that the RelA subunit of nuclear factor κB (NF-κB/RelA) is necessary for the inhibition of TGF-β-induced phosphorylation, nuclear translocation, and DNA binding of SMAD signaling complexes by tumor necrosis factor-α (TNF-α). The antagonism is mediated through up-regulation of Smad7 synthesis and induction of stable associations between ligand-activated TGF-β receptors and inhibitory Smad7. Down-regulation of endogenous Smad7 by expression of antisense mRNA releases TGF-β/SMAD-induced transcriptional responses from suppression by cytokine-activated NF-κB/RelA. Following stimulation with bacterial lipopolysaccharide (LPS), or the proinflammatory cytokines TNF-α and interleukin-1β (IL-1β, NF-κB/RelA induces Smad7 synthesis through activation of Smad7 gene transcription. These results suggest a mechanism of suppression of TGF-β/SMAD signaling by opposing stimuli mediated through the activation of inhibitory Smad7 by NF-κB/RelA.

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 Propofol attenuated the effect of TNF-α on occludin expression by inhibiting HIF-1α/VEGF/VEGFR-2/ERK signaling pathway in hCMEC/D3 cells

2019 ◽  
Author(s):  
Yue Zhang ◽  
Xiaowei Ding ◽  
Changhong Miao ◽  
Jiawei Chen
Keyword(s):  
Signaling Pathway ◽  
Cell Counting ◽  
Erk Signaling ◽  
Microvascular Endothelial Cell ◽  
Tight Junction Proteins ◽  
Tnf Α ◽  
Underlying Mechanisms ◽  
Factor Α ◽  
Necrosis Factor ◽  
Junction Proteins

Abstract Purpose: The levels of tight junction proteins (TJs), especially occludin, correlate with blood-brain barrier (BBB) disruption caused by inflammation in central nervous system (CNS). It has been reported that propofol, the most commonly used anesthetic, could inhibit inflammation response in CNS. In this study, we investigated the effects of tumor necrosis factor-α(TNF-α) and propofol on occludin expression in human cerebral microvascular endothelial cell line, D3 clone (hCMEC/D3 cells), and explored the underlying mechanisms. Methods: The hCMEC/D3 cells were treated with propofol, followed by TNF-α. The expression and phosphorylation of Hif-1α, VEGF, VEGFR-2, ERK, p38MAPK and occludin were measured by Western blot analysis. The cell viability of hCMEC/D3 cells was measured by cell counting kit-8. Results: TNF-α (10 ng/ml, 4 h) significantly decreased the expression of occludin, which was attenuated by propofol (25 μM). TNF-α induced Hif-1α/VEGF/VEGFR-2/ERK signaling pathway, while propofol could inhibit it. TNF-α induced the phosphorylation of p38MAPK, while propofol had no effect on it. In addition, the inhibitors of Hif-1α, VEGF, VEGFR-2, and ERK could reduce the effect of TNF-α on occludin expression. Conclusion: TNF-α could decrease the expression of occludin via activating Hif-1α/VEGF/VEGFR-2/ERK signaling pathway, which was attenuated by propofol.

scholarly journals Antioxidant and Anti-Inflammatory Potential of Thymoquinone and Lycopene Mitigate the Chlorpyrifos-Induced Toxic Neuropathy

2021 ◽  
Vol 14 (9) ◽  
pp. 940
Author(s):  
Mohamed Aboubakr ◽  
Said M. Elshafae ◽  
Ehab Y. Abdelhiee ◽  
Sabreen E. Fadl ◽  
Ahmed Soliman ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Corn Oil ◽  
Organophosphate Pesticide ◽  
Toxic Neuropathy ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Factor Α ◽  
Apoptotic Effects ◽  
Oxidative State ◽  
Necrosis Factor

CPF (chlorpyrifos) is an organophosphate pesticide used in agricultural and veterinary applications. Our experiment aimed to explore the effects of thymoquinone (TQ) and/or lycopene (LP) against CPF-induced neurotoxicity. Wistar rats were categorized into seven groups: first group served as a control (corn oil only); second group, TQ (10 mg/kg); third group, LP (10 mg/kg); fourth group, CPF (10 mg/kg) and deemed as CPF toxic control; fifth group, TQ + CPF; sixth group, (LP + CPF); and seventh group, (TQ + LP + CPF). CPF intoxication inhibited acetylcholinesterase (AchE), decreased glutathione (GSH) content, and increased levels of malondialdehyde (MDA), an oxidative stress biomarker. Furthermore, CPF impaired the activity of antioxidant enzymes including superoxide dismutase (SOD) and catalase (CAT) along with enhancement of the level of inflammatory mediators such as tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1β. CPF evoked apoptosis in brain tissue. TQ or LP treatment of CPF-intoxicated rats greatly improved AchE activity, oxidative state, inflammatory responses, and cell death. Co-administration of TQ and LP showed better restoration than their sole treatment. In conclusion, TQ or LP supplementation may alleviate CPF-induced neuronal injury, most likely due to TQ or LPs’ antioxidant, anti-inflammatory, and anti-apoptotic effects.

Shiga Toxin Type 1 Activates Tumor Necrosis Factor-α Gene Transcription and Nuclear Translocation of the Transcriptional Activators Nuclear Factor-κB and Activator Protein-1

Blood ◽  
1998 ◽  
Vol 92 (2) ◽  
pp. 558-566 ◽  
Author(s):  
Ramesh Sakiri ◽  
Belakere Ramegowda ◽  
Vernon L. Tesh
Keyword(s):  
Endothelial Cells ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Nuclear Translocation ◽  
Vascular Lesions ◽  
Transcriptional Activators ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Shiga toxins (Stxs) produced by Shigella dysenteriae 1 andEscherichia coli have been implicated in the pathogenesis of bloody diarrhea, acute renal failure, and neurologic abnormalities. The pathologic hallmark of Stx-mediated tissue damage is the development of vascular lesions in which endothelial cells are swollen and detached from underlying basement membranes. However, in vitro studies using human vascular endothelial cells demonstrated minimal Stx-induced cytopathic effects, unless the target cells were also incubated with the proinflammatory cytokines tumor necrosis factor-α (TNF-α) or interleukin-1β (IL-1β). These cytokines have been shown to upregulate the expression of the Stx-binding membrane glycolipid globotriaosylceramide (Gb3). We show here that purified Stx1 induces TNF secretion by a human monocytic cell line, THP-1, in a dose- and time-dependent manner. Treatment of cells with both lipopolysaccharides (LPS) and Stx1 results in augmented TNF production. Treatment with the nontoxic Gb3-binding subunit of Stx1 or with an anti-Gb3 monoclonal antibody did not trigger TNF production. Northern blot analyses show that Stx1 causes increased TNF-α production through transcriptional activation. Increased levels of TNF-α mRNA are preceded by the nuclear translocation of the transcriptional activators NF-κB and AP-1 and the loss of cytoplasmic IκB-α. These data are the first to show that, in addition to direct cytotoxicity, Stxs possess cellular signaling capabilities sufficient to induce the synthesis of cytokines that may be necessary for target cell sensitization and the development of vascular lesions.

scholarly journals Design of a 3D BMP-2-Delivering Tannylated PCL Scaffold and Its Anti-Oxidant, Anti-Inflammatory, and Osteogenic Effects In Vitro

2018 ◽  
Vol 19 (11) ◽  
pp. 3602 ◽  
Author(s):  
Jae Lee ◽  
Hyunwoong Lim ◽  
Jae Ahn ◽  
Dongsik Jang ◽  
Seung Lee ◽  
...  
Keyword(s):  
Three Dimensional ◽  
Calcium Deposition ◽  
Mrna Levels ◽  
Tnf Α ◽  
Anti Oxidant ◽  
Anti Inflammatory ◽  
Factor Α ◽  
Bone Morphogenic Protein 2 ◽  
Necrosis Factor

In this study, a novel three-dimensional (3D) bone morphogenic protein-2 (BMP-2)-delivering tannylated polycaprolactone (PCL) (BMP-2/tannic acid (TA)/PCL) scaffold with anti-oxidant, anti-inflammatory, and osteogenic activities was fabricated via simple surface coating with TA, followed by the immobilization of BMP-2 on the TA-coated PCL scaffold. The BMP-2/TA/PCL scaffold showed controlled and sustained BMP-2 release. It effectively scavenged reactive oxygen species (ROS) in cells, and increased the proliferation of MC3T3-E1 cells pre-treated with hydrogen peroxide (H2O2). Additionally, the BMP-2/TA/PCL scaffold significantly suppressed the mRNA levels of pro-inflammatory cytokines, including matrix metalloproteinases-3 (MMP-3), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), in lipopolysaccharide (LPS)-induced MC3T3-E1 cells. Furthermore, it showed outstanding enhancement of the osteogenic activity of MC3T3-E1 cells through increased alkaline phosphatase (ALP) activity and calcium deposition. Our findings demonstrated that the BMP-2/TA/PCL scaffold plays an important role in scavenging ROS, suppressing inflammatory response, and enhancing the osteogenic differentiation of cells.

Role of extracellular superoxide in neutrophil activation: interactions between xanthine oxidase and TLR4 induce proinflammatory cytokine production

2008 ◽  
Vol 294 (4) ◽  
pp. C985-C993 ◽  
Author(s):  
Emmanuel Lorne ◽  
Jaroslaw W. Zmijewski ◽  
Xia Zhao ◽  
Gang Liu ◽  
Yuko Tsuruta ◽  
...  
Keyword(s):  
Xanthine Oxidase ◽  
Nuclear Translocation ◽  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
Nuclear Factor Κb ◽  
Neutrophil Activation ◽  
Limited Information ◽  
Inhibitory Protein ◽  
Tnf Α ◽  
Factor Α

Reactive oxygen species (ROS) contribute to neutrophil activation and the development of acute inflammatory processes in which neutrophils play a central role. However, there is only limited information concerning the mechanisms through which extracellular ROS, and particularly cell membrane-impermeable species, such as superoxide, enhance the proinflammatory properties of neutrophils. To address this issue, neutrophils were exposed to superoxide generating combinations of xanthine oxidase and hypoxanthine or lumazine. Extracellular superoxide generation induced nuclear translocation of nuclear factor-κB (NF-κB) and increased neutrophil production of the NF-κB-dependent cytokines tumor necrosis factor-α (TNF-α) and macrophage inhibitory protein-2 (MIP-2). In contrast, there were no changes in TNF-α or MIP-2 expression when neutrophils lacking Toll-like receptor-4 (TLR4) were exposed to extracellular superoxide. Immunoprecipitation, confocal microscopy, and fluorescence resonance energy transfer (FRET) studies demonstrated association between TLR4 and xanthine oxidase. Exposure of neutrophils to heparin attenuated binding of xanthine oxidase to the cell surface as well as interactions with TLR4. Heparin also decreased xanthine oxidase-induced nuclear translocation of NF-κB as well as production of proinflammatory cytokines. These results demonstrate that extracellular superoxide has proinflammatory effects on neutrophils, predominantly acting through an TLR4-dependent mechanism that enhances nuclear translocation of NF-κB and increases expression of NF-κB-dependent cytokines.

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