The pro-inflammatory cytokines IFNγ/TNFα increase chromogranin A-positive neuroendocrine cells in the colonic epithelium

2016 ◽  
Vol 473 (21) ◽  
pp. 3805-3818 ◽  
Author(s):  
José Antonio Hernández-Trejo ◽  
Dimelza Suárez-Pérez ◽  
Itzel Zenidel Gutiérrez-Martínez ◽  
Omar Eduardo Fernandez-Vargas ◽  
Carolina Serrano ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Chromogranin A ◽  
Colonic Mucosa ◽  
Interferon Γ ◽  
The Body ◽  
Neuroendocrine Cells ◽  
Proliferating Cells ◽  
Tensin Homolog ◽  
Factor Α ◽  
Pro Inflammatory Cytokines

The gastrointestinal tract is the largest hormone-producing organ in the body due to a specialized cell population called enteroendocrine cells (EECs). The number of EECs increases in the mucosa of inflammatory bowel disease patients; however, the mechanisms responsible for these changes remain unknown. Here, we show that the pro-inflammatory cytokines interferon γ (IFNγ) and tumor necrosis factor α (TNFα) or dextran sulfate sodium (DSS)-induced colitis increase the number of EECs producing chromogranin A (CgA) in the colonic mucosa of C57BL/6J mice. CgA-positive cells were non-proliferating cells enriched with inactive phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and autophagy markers. Moreover, inhibition of Akt and autophagy prevented the increase in CgA-positive cells after IFNγ/TNFα treatment. Similarly, we observed that CgA-positive cells in the colonic mucosa of patients with colitis expressed Akt and autophagy markers. These findings suggest that Akt signaling and autophagy control differentiation of the intestinal EEC lineage during inflammation.

scholarly journals Antidepressant-Like Effect and Mechanism of Action of Honokiol on the Mouse Lipopolysaccharide (LPS) Depression Model

Molecules ◽  
2019 ◽  
Vol 24 (11) ◽  
pp. 2035 ◽  
Author(s):  
Bo Zhang ◽  
Ping-Ping Wang ◽  
Kai-Li Hu ◽  
Li-Na Li ◽  
Xue Yu ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Mechanism Of Action ◽  
Tail Suspension Test ◽  
Interferon Γ ◽  
Biologically Active ◽  
Free Calcium ◽  
Immobility Time ◽  
Anti Inflammatory ◽  
Factor Α ◽  
Pro Inflammatory Cytokines

There is growing evidence that neuroinflammation is closely linked to depression. Honokiol, a biologically active substance extracted from Magnolia officinalis, which is widely used in traditional Chinese medicine, has been shown to exert significant anti-inflammatory effects and improve depression-like behavior caused by inflammation. However, the specific mechanism of action of this activity is still unclear. In this study, the lipopolysaccharide (LPS) mouse model was used to study the effect of honokiol on depression-like behavior induced by LPS in mice and its potential mechanism. A single administration of LPS (1 mg/kg, intraperitoneal injection) increased the immobility time in the forced swimming test (FST) and tail suspension test (TST), without affecting autonomous activity. Pretreatment with honokiol (10 mg/kg, oral administration) for 11 consecutive days significantly improved the immobility time of depressed mice in the FST and TST experiments. Moreover, honokiol ameliorated LPS-induced NF-κB activation in the hippocampus and significantly reduced the levels of the pro-inflammatory cytokines; tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), and interferon γ (IFN-γ). In addition, honokiol inhibited LPS-induced indoleamine 2,3-dioxygenase (IDO) activation and quinolinic acid (a toxic product) increase and reduced the level of free calcium in brain tissue, thereby inhibiting calcium overload. In summary, our results indicate that the anti-depressant-like effects of honokiol are mediated by its anti-inflammatory effects. Honokiol may inhibit the LPS-induced neuroinflammatory response through the NF-κB signaling pathway, reducing the levels of related pro-inflammatory cytokines, and furthermore, this may affect tryptophan metabolism and increase neuroprotective metabolites.

scholarly journals Serum Levels of Pro-inflammatory Cytokines in relationship to outcomes in Children with P. falciparum malaria, in Nnewi-South east Nigeria

1970 ◽  
Vol 42 (2) ◽  
pp. 142-146
Author(s):  
EC Okocha ◽  
NC Ibeh ◽  
EO Ukaejiofor ◽  
JC Ebenebe ◽  
JC Aneke ◽  
...  
Keyword(s):  
Immune Response ◽  
Platelet Count ◽  
Falciparum Malaria ◽  
Inflammatory Cytokines ◽  
Parasite Density ◽  
The Body ◽  
World Health ◽  
Inadequate Response ◽  
Monocyte Count ◽  
Pro Inflammatory Cytokines

Background and Objective: In P. falciparum malaria (PFM) infestation there are marked changes in cytokine production as the body mounts an immune response to it. Hence we set out to study these changes.Methods: A total of 158 cases of PFM among children attending the paediatric unit of our hospital and 56 healthy controls were studied. Children with febrile illness were screened for malaria using 10% Giemsa stained blood smear. Patients with positive smears were recruited; co-infected patients – those infected by another organism in addition to plasmodium specie.- were excluded. Whole blood was collected, some into plain tubes for serum cytokine testing and some into EDTA bottles for complete blood count and parasite density (PD) determination. Controls with asymptomatic parasitaemia were excluded.Results: Using the World Health Organization criteria for defining severe malaria; we identified 15 cases of severe and 143 cases of uncomplicated PFM. Significantly elevated levels of interleukin-1 (IL-1), interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-α) were seen in the uncomplicated and severe forms of PFM. It was observed that the elevated cytokine values correlated with PD (in uncomplicated PFM but not in the severe forms). The difference between PD/absolute monocyte count (AMC) ratio was not significant (p=0.13); while PD/platelet count (PC) and PC/ AMC ratios were significant (p=0.01, and 0.03 respectively) when compared between uncomplicated and severe disease.Conclusion: Our data seems to suggest that subjects with an adequate immune response to the parasite density, in terms of pro-inflammatory cytokine levels, presented with uncomplicated disease; while those who have an inadequate response presented with severe disease. The ratios of (PD/PC) and (PC/AMC), in the positive and negative directions respectively, may be predictors of increased disease severity. These observations may have implications for predicting disease outcome and PFM therapy.Key Words: plasmodium falciparum malaria, pro-inflammatory cytokines, Parasite density/Platelet count ratio, Platelet count/Absolute monocyte

scholarly journals Depletion of iNOS-derived nitric oxide by prostaglandin H synthase-2 in inflammation-activated J774.2 macrophages through lipohydroperoxidase turnover

2005 ◽  
Vol 385 (3) ◽  
pp. 815-821 ◽  
Author(s):  
Stephen R. CLARK ◽  
Peter B. ANNING ◽  
Marcus J. COFFEY ◽  
Andrew G. ROBERTS ◽  
Lawrence J. MARNETT ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Inflammatory Cytokines ◽  
Mammalian Cells ◽  
Biological Effects ◽  
Interferon Γ ◽  
Dependent Manner ◽  
Prostaglandin H Synthase ◽  
Prostaglandin H ◽  
20 Nm ◽  
Pro Inflammatory Cytokines

PGHS-2 (prostaglandin H synthase-2) is induced in mammalian cells by pro-inflammatory cytokines in tandem with iNOS [high-output (‘inducible’) nitric oxide synthase], and is co-localized with iNOS and nitrotyrosine in human atheroma macrophages. Herein, murine J774.2 macrophages incubated with lipopolysaccharide and interferon γ showed induction of PGHS-2 and generated NO using iNOS that could be completely depleted by 12(S)-HPETE [12(S)-hydroperoxyeicosatetraenoic acid; 2.4 μM] or hydrogen peroxide (500 μM) (0.42±0.084 and 0.38±0.02 nmol·min−1·106 cells−1 for HPETE and H2O2 respectively). COS-7 cells transiently transfected with human PGHS-2 also showed HPETE- or H2O2-dependent NO decay (0.44±0.016 and 0.20±0.04 nmol·min−1·106 cells−1 for 2.4 μM HPETE and 500 μM H2O2 respectively). Finally, purified PGHS-2 consumed NO in the presence of HPETE or H2O2 (168 and 140 μM·min−1·μM enzyme−1 for HPETE and H2O2 respectively), in a haem-dependent manner, with 20 nM enzyme consuming up to 4 μM NO. Km (app) values for NO and 15(S)-HPETE were 1.7±0.2 and 0.45±0.16 μM respectively. These data indicate that PGHS-2 catalytically consumes NO during peroxidase turnover and that pro-inflammatory cytokines simultaneously upregulate NO synthesis and degradation pathways in murine macrophages. Catalytic NO consumption by PGHS-2 represents a novel interaction between NO and PGHS-2 that may impact on the biological effects of NO in vascular signalling and inflammation.

Agrimonia pilosa Ledeb Root Extract: Anti-Inflammatory Activities of the Medicinal Herb in LPS-Induced Inflammation

2020 ◽  
Vol 48 (08) ◽  
pp. 1875-1893
Author(s):  
Da-Sol Kim ◽  
Kyoung-Eun Park ◽  
Yeon-Ju Kwak ◽  
Moon-Kyoung Bae ◽  
Soo-Kyung Bae ◽  
...  
Keyword(s):  
Porphyromonas Gingivalis ◽  
Inflammatory Cytokines ◽  
Mapk Signaling ◽  
The Body ◽  
Raw 264.7 Cells ◽  
Root Extract ◽  
Raw 264.7 ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

Inflammation regulation is essential for maintaining healthy functions and normal homeostasis of the body. Porphyromonas gingivalis (P. gingivalis) is a gram-negative anaerobic bacterium and a major pathogen that causes oral inflammation and other systemic inflammations. This study aims to examine the anti-inflammatory effects of Agrimonia pilosa Ledeb root extracts (APL-ME) in Porphyromonas gingivalis LPS-induced RAW 264.7 cells and find anti-inflammatory effect compounds of APL-ME. The anti-inflammatory effects of APL-ME were evaluated anti-oxidant activity, cell viability, nitrite concentration, pro-inflammatory cytokines (interleukin-1[Formula: see text], interleukin-6, tumor necrosis factor (TNF)-[Formula: see text], and anti-inflammatory cytokine (interleukin-10 (IL-10)). Also, Inflammation related genes and proteins, cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS), expression were decreased by APL-ME and mitogen-activated protein kinase (MAPK) signaling proteins expression was regulated by APL-ME. Liquid chromatography-mass spectrometer (LC/MS)-MS analysis results indicated that several components were detected in APL-ME. Our study indicated that APL-ME suppressed nitrite concentrations, pro-inflammatory cytokines such as IL-1[Formula: see text], IL-6 and TNF-[Formula: see text] in P. gingivalis LPS induced RAW 264.7 cells. However, IL-10 expression was increased by ALP-ME. In addition, protein expressions of COX-2 and iNOS were inhibited APL-ME extracts dose-dependently. According to these results, APL-ME has anti-inflammatory effects in P. gingivalis LPS induced RAW 264.7 cells.

scholarly journals HIF1α/TET1 Pathway Mediates Hypoxia-Induced Adipocytokine Promoter Hypomethylation in Human Adipocytes

Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 134 ◽  
Author(s):  
Mohamed M. Ali ◽  
Shane A. Phillips ◽  
Abeer M. Mahmoud
Keyword(s):  
Dna Methylation ◽  
Interleukin 1 ◽  
Hypoxia Inducible Factor ◽  
Interferon Γ ◽  
The Body ◽  
Human Adipocytes ◽  
Protein Levels ◽  
Factor Α ◽  
Necrosis Factor

Obesity is associated with the accumulation of dysfunctional adipose tissue that secretes several pro-inflammatory cytokines (adipocytokines). Recent studies have presented evidence that adipose tissues in obese individuals and animal models are hypoxic, which may result in upregulation and stabilization of the hypoxia inducible factor HIF1α. Epigenetic mechanisms such as DNA methylation enable the body to respond to microenvironmental changes such as hypoxia and may represent a mechanistic link between obesity-associated hypoxia and upregulated inflammatory adipocytokines. The purpose of this study was to investigate the role of hypoxia in modifying adipocytokine DNA methylation and subsequently adipocytokine expression. We suggested that this mechanism is mediated via the DNA demethylase, ten-eleven translocation-1 (TET1), transcription of which has been shown to be induced by HIF1α. To this end, we studied the effect of hypoxia (2% O2) in differentiated subcutaneous human adipocytes in the presence or absence of HIF1α stabilizer (Dimethyloxalylglycine (DMOG), 500 μM), HIF1α inhibitor (methyl 3-[[2-[4-(2-adamantyl) phenoxy] acetyl] amino]-4-hydroxybenzoate, 30 μM), or TET1-specific siRNA. Subjecting the adipocytes to hypoxia significantly induced HIF1α and TET1 protein levels. Moreover, hypoxia induced global hydroxymethylation, reduced adipocytokine DNA promoter methylation, and induced adipocytokine expression. These effects were abolished by either HIF1α inhibitor or TET1 gene silencing. The major hypoxia-responsive adipocytokines were leptin, interleukin-1 (IL6), IL1β, tumor necrosis factor α (TNFα), and interferon γ (IFNγ). Overall, these data demonstrate an activation of the hydroxymethylation pathway mediated by TET1. This pathway contributes to promoter hypomethylation and gene upregulation of the inflammatory adipocytokines in adipocytes in response to hypoxia.

scholarly journals Sudachinoid- and Ichangensin-Type Limonoids from Citrus junos Downregulate Pro-Inflammatory Cytokines

2020 ◽  
Vol 21 (18) ◽  
pp. 6963
Author(s):  
Jihun Shin ◽  
Hwa Young Song ◽  
Mina Lee
Keyword(s):  
Inflammatory Cytokines ◽  
Human Colon ◽  
Dominant Group ◽  
Citrus Junos ◽  
Mouse Macrophages ◽  
Inflammatory Bowel ◽  
Anti Inflammatory ◽  
Factor Α ◽  
Necrosis Factor ◽  
Pro Inflammatory Cytokines

Limonoids, a dominant group of phytochemicals in the Rutaceae family, are known to exhibit several pharmacological activities. To identify natural products having efficacy against inflammatory bowel disease (IBD), we isolated 13 limonoids including a new compound, methyl sudachinoid A, from the seeds of Citrus junos and investigated their anti-inflammatory effects by assessing the expression of pro-inflammatory cytokines in lipopolysaccharide-stimulated RAW 264.7 mouse macrophages and HT-29 human colon epithelial cells. Our findings revealed that limonoids significantly downregulated the pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor-α, and nuclear transcription factor κB. In particular, sudachinoid-type compounds, methyl sudachinoid A and sudachinoid B, and ichangensin-type compound, 1-O-methyichangensin downregulated the expression of pro-inflammatory cytokines more potently than other limonoids, nomilin and limonin, which have been previously reported to exhibit anti-inflammatory activities in other cells; nomilin and limonin were therefore employed as positive controls in this study. Herein, we reveal that the anti-inflammatory activities of limonoids including a new compound methyl sudachinoid A from C. junos were mediated via the downregulation of pro-inflammatory cytokines and these limonoids can be employed as potential therapeutic phytochemicals for IBD.

scholarly journals Pro-inflammatory cytokines increase glucose, alanine and triacylglycerol utilization but inhibit insulin secretion in a clonal pancreatic β-cell line

2007 ◽  
Vol 195 (1) ◽  
pp. 113-123 ◽  
Author(s):  
Aoife Kiely ◽  
Neville H McClenaghan ◽  
Peter R Flatt ◽  
Philip Newsholme
Keyword(s):  
Insulin Secretion ◽  
Inflammatory Cytokines ◽  
Prolonged Exposure ◽  
Cell Metabolism ◽  
Glutamate Release ◽  
Β Cell ◽  
Catabolic State ◽  
Stimulus Secretion Coupling ◽  
Factor Α ◽  
Pro Inflammatory Cytokines

We have investigated the effects of prolonged exposure (24 h) to pro-inflammatory cytokines on β-cell metabolism and insulin secretion using clonal BRIN-BD11 β cells. Addition of IL-1β, tumour necrosis factor-α and IFN-γ (at concentrations that did not induce apoptosis) inhibited chronic (24 h) and acute stimulated levels of insulin release (by 59 and 93% respectively), increased cellular glucose and alanine consumption, and also elevated lactate and glutamate release. However, ATP levels and cellular triacylglycerol were decreased while glutathione was increased. We conclude that sub-lethal concentrations of pro-inflammatory cytokines appear to shift β-cell metabolism away from a key role in energy generation and stimulus–secretion coupling and towards a catabolic state which may be related to cell defence.

scholarly journals Immunomodulatory Responses Of Toll Like Receptors Against 2019nCoV

2021 ◽  
Vol 10 (2) ◽  
Author(s):  
Amany Sayed Maghraby
Keyword(s):  
Inflammatory Cytokines ◽  
English Language ◽  
Toll Like Receptors ◽  
Complex Molecules ◽  
Ribonucleic Acids ◽  
Histocompatibility Complex ◽  
Tnf Α ◽  
Factor Α ◽  
Molecular Signals ◽  
Pro Inflammatory Cytokines

The present review discusses the immune signals via toll like receptors (TLRs) against 2019nCoV. We researched using different database, up to June 18th, 2020. All the included articles were published in English language. The outcome of this review, that some TLRs agonists or antagonists are progressed as drugs to combat and down regulating TLRs immune signals respectively. TLRs 3 and 4 recognized 2019nCoV spike protein through immune and molecular signals that leading to immune stimulation of pro-inflammatory cytokines and even the immune fever. While the TLRs7 and 8 recognized single-stranded ribonucleic acids (ssRNAs) leading to elevation of the tumour necrosis factor α (TNF-α), interleukin (IL)-6 and -12 levels. TLRs agonists or antagonists utilized as immunotherapeutic targets against 2019nCoV via TLRs signals. Chloroquine and hydroxychloroquine; the approval compounds for 2019nCoV therapy can be inhibiting the class II major histocompatibility complex molecules expression and antigen presentation and even immune suppressions of the pro-inflammatory cytokines profile.

scholarly journals The effect of hemantane on the level of pro-inflammatory cytokines in the nigrocaudate complex of the brain of mice with experimental parkinsonism

2021 ◽  
pp. 45-49
Author(s):  
Н.А. Воронина ◽  
В.Г. Кучеряну ◽  
Л.А. Ветрилэ ◽  
В.В. Голоборщева ◽  
И.Г. Капица ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Clinical Stage ◽  
Late Phase ◽  
Brain Structures ◽  
Interferon Γ ◽  
Nigrostriatal System ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tnf Α ◽  
Ifn Γ ◽  
Pro Inflammatory Cytokines

Целью данных исследований явилось изучение влияния гимантана (N-(2-адамантил)-гексаметиленимина гидрохлорида) на уровень провоспалительных цитокинов IL-1β, IL-6, интерферона-γ (ИФН-γ) и фактора некроза опухоли-α (ФНО-α) в нигрокаудатном комплексе мышей на ранней и поздней клинической фазе экспериментального паркинсонического синдрома (ПС), для выяснения его антипаркинсонического эффекта. Методы исследования: Раннюю и позднюю клиническую фазу ПС создавали у мышей линии C57BL/6J внутрибрюшинным введением пронейротоксина 1-метил-4-фенил-1,2,3,6-тетрагидропиридина (МФТП) в дозах 12 мг/кг или 20 мг/кг по 4 инъекции с интервалом 2 часа, соответственно. Гимантан вводили мышам внутрибрюшинным в дозе 20 мг/кг, предварительно каждый раз за 30 мин до введения МФТП. Содержание цитокинов в структурах мозга мышей определяли методом иммуноферментного анализа с использованием тест-систем производства «Cloud-Clone Corporation», США и считывающего устройства «ИФА-reader» прибора «ImmunoChem-2100», США. Результаты: Показано, что уровень IL-1β, IL-6, ИФН-γ и ФНО-α в нигрокаудатном комплексе мозга мышей возрастает как на ранней, так и на поздней фазах развития ПС. Предварительное применение гимантана снижало в нигрокаудатном комплексе мышей содержание цитокинов IL-1β, ИФН-γ и ФНО-α на ранней фазе, и только одного из 4 изученных (IL-6) - на поздней фазе развития ПС. Предполагается, что антипаркинсонический эффект гимантана на ранней клинической стадии МФТП-индуцированного ПС осуществляется, в том числе, за счёт снижения уровня провоспалительных цитокинов в нигростриатной системе, предупреждая снижение жизнеспособности дофаминергических нейронов. The aim of this work was to study the effect of Hemantane (N-(2-adamantyl)-hexamethyleneimine hydrochloride) on the level of pro-inflammatory cytokines IL-1β, IL-6, interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α) in the nigrocaudate complex of mice in early and late clinical phases of experimental Parkinsonian syndrome (PS) to elucidate its antiparkinsonian effect. Material and methods: The early and late clinical phases of PS were created in C57BL / 6J mice by 4 intraperitoneal injections at 2-h intervals of a proneurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), at a dose of 12 mg/kg or 20 mg/kg. Hemantane was injected intraperitoneally at a dose of 20 mg/kg 30 min before each MPTP administration. Concentrations of cytokines in mouse brain structures were measured by enzyme-linked immunosorbent assay (ELISA) using Cloud-Clone Corporation (USA) test systems and an ImmunoChem-2100 (USA) ELISA reader. Results: Concentrations of IL-1β, IL-6, IFN-γ, and TNF-α in the nigrocaudate complex were increased both in the early and late phases of PS. Prior administration of hemantane reduced the content of IL-1β, IFN-γ, and TNF-α in the nigrocaudate complex at the early phase and the content of only one of the 4 studied cytokines (IL-6) at the late phase of PS. It was assumed that the antiparkinsonian effect of hemantane at the early clinical stage of MPTP-induced PS involves a decrease in proinflammatory cytokines in the nigrostriatal system, which prevents the impairment of the viability of dopaminergic neurons.

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