scholarly journals Downregulation of Cytokines and Chemokines By GB Virus C after Transfusion-Transmission in HIV+ Blood Recipients

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4122-4122
Author(s):  
Marion Lanteri ◽  
Farnaz Vahidnia ◽  
Sylvia Tan ◽  
Jack Stapleton ◽  
Philip J. Norris ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Pathway Analysis ◽  
Myeloid Cells ◽  
Host Immune System ◽  
Cytokines And Chemokines ◽  
Cell Counts ◽  
Significant Difference ◽  
Anti Inflammatory ◽  
The Impact ◽  
Pro Inflammatory Cytokines

Abstract Background: An association between GBV-C and improved HIV-infection outcome has been reported in HIV+ individuals with active GBV-C co-infection. The host immunological response underlying GBV-C and HIV co-infection that results in better HIV survival is not well characterized. This longitudinal study provides insight into the immune mechanisms underlying the potential protective role of GBV-C in HIV infected patients. Methods: Concentrations of 64 cytokines and chemokines were measured in plasma samples from the Viral Activation Transfusion Study (VATS) cohort before and longitudinally after GBV-C acquisition in 30 HIV+/GBV-C+ cases and 30 HIV+/GBV-C- controls up to 15 months following first transfusion. Adjusted mixed modeling was used to analyze the impact of GBV-C infection on cytokine/chemokine concentrations over time, adjusting for time elapsed, HAART treatment status, HIV VL, and subject. Pathway Analysis (PA; Qiagen Ingenuity Pathway Analysis) was performed to help predict what effect the observed cytokine changes might have on the host immune system. Results: A significant decrease in HIV VL was observed in HIV+/GBV-C+ cases from a mean log10(HIV VL) = 4.33 at baseline down to 3.24 at 100 days post-GBV-C detection (p<0.01) and maintained at 3.39 at 300 days post-GBV-C detection (p=0.02). GBV-C+/HIV+ cases had higher CD4 T cell counts than controls after acquisition of GBV-C infection. At baseline, there was no significant difference between HIV+/GBV-C+ cases and HIV+/GBV-C- controls in cytokine/chemokine levels. Most of the modulated cytokines and chemokines were reduced post-GBV-C detection, including many pro-inflammatory cytokines, suggesting an overall anti-inflammatory effect of GBV-C after co-infection in HIV+ subjects (Figure 1). After adjustment for HIV VL and HAART status, GBV-C infection significantly associated with decreases in the levels of nine cytokines (p<0.05 and FDR≤0.2): one anti-inflammatory cytokines IL-10 , two pro-inflammatory cytokines IL-6 and IL-7, four chemo-attractants MIP-1α, 6Ckine, I-TAC and GCP-2, and the growth factor SCF (Figure 2). Pathway Analysis showed HIV+/GBV-C+ cases had an enrichment in genes associated with cell death and apoptosis pathways of various cells (phagocytes, leukocytes including T cells, myeloid cells, dendritic cells, granulocytes, APC, neutrophils, neuroglia) and in the development of phagocytes and function of APCs and a decrease in binding, migration, and movement of cells within 3 months post-GBV-C detection. Similarly, 300 days post-GBV-C detection, there was a further decrease in cellular activation (PBMCs, myeloid cells) and cellular trafficking with an increase in the proliferation of myeloid progenitor cells and leukocyte infection. Conclusion: GBV-C has a protective effect in part through a competition mechanism leading to decreased inflammation and improved HIV disease outcome in GBV-C+/HIV+ individuals. Further studies are necessary to establish whether this purportedly non-pathogenic virus causing immune down-regulation could have deleterious effects on the host at the cellular level, including depleting the cells which are HIV targets. Figure 1. Figure 1. Figure 2. Figure 2. Disclosures No relevant conflicts of interest to declare.

scholarly journals Oral feeding with probiotic Lactobacillus rhamnosus attenuates cigarette smoke-induced COPD in C57Bl/6 mice: Relevance to inflammatory markers in human bronchial epithelial cells

2019 ◽  
Author(s):  
J.L. Carvalho ◽  
M. Miranda ◽  
A.K. Fialho ◽  
H. Castro-Faria-Neto ◽  
E. Anatriello ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Cigarette Smoke ◽  
Inflammatory Cytokines ◽  
Lactobacillus Rhamnosus ◽  
Bronchial Epithelial Cells ◽  
Human Bronchial Epithelial Cells ◽  
Bronchial Epithelial ◽  
Cytokines And Chemokines ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

AbstractCOPD is a prevalent lung disease with significant impacts on public health. Affected airways exhibit pulmonary neutrophilia and consequent secretion of pro-inflammatory cytokines and proteases, which result in lung emphysema. Probiotics act as nonspecific modulators of the innate immune system that improve several inflammatory responses. To investigate the effect of Lactobacillus rhamnosus (Lr) on cigarette smoke (CS)-induced COPD C57Bl/6 mice were treated with Lr during the week before COPD induction and three times/week until euthanasia. For in vitro assays, murine bronchial epithelial cells as well as human bronchial epithelial cells exposed to cigarette smoke extract during 24 hours were treated with Lr 1 hour before CSE addition. Lr treatment attenuated the inflammatory response both in the airways and lung parenchyma, reducing neutrophilic infiltration and the production of pro-inflammatory cytokines and chemokines. Also, Lr-treated mice presented with lower metalloproteases in lung tissue and lung remodeling. In parallel to the reduction in the expression of TLR2, TLR4, TLR9, STAT3, and NF-κB in lung tissue, Lr increased the levels of IL-10 as well as SOCS3 and TIMP1/2, indicating the induction of an anti-inflammatory environment. Similarly, murine bronchial epithelial cells as well as human bronchial epithelial cells (BEAS) exposed to CSE produced pro-inflammatory cytokines and chemokines, which were inhibited by Lr treatment in association with the production of anti-inflammatory molecules. Moreover, the presence of Lr also modulated the expression of COPD-associated transcription found into BALF of COPD mice group, i.e., Lr downregulated expression of NF-κB and STAT3, and inversely upregulated increased expression of SOCS3. Thus, our findings indicate that Lr modulates the balance between pro- and anti-inflammatory cytokines in human bronchial epithelial cells upon CS exposure and it can be a useful tool to improve the lung inflammatory response associated with COPD.

scholarly journals Nobiletin exerts anti-diabetic and anti-inflammatory effects in an in vitro human model and in vivo murine model of gestational diabetes

2020 ◽  
Vol 134 (6) ◽  
pp. 571-592 ◽  
Author(s):  
Caitlyn Nguyen-Ngo ◽  
Carlos Salomon ◽  
Stephanie Quak ◽  
Andrew Lai ◽  
Jane C Willcox ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Glucose Metabolism ◽  
Gestational Diabetes ◽  
Mrna Expression ◽  
Inflammatory Cytokines ◽  
Cytokines And Chemokines ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

Abstract Gestational diabetes mellitus (GDM) is a global health issue, whereby pregnant women are afflicted with carbohydrate intolerance with first onset during pregnancy. GDM is characterized by maternal peripheral insulin resistance, thought to be driven by low-grade maternal inflammation. Nobiletin, a polymethoxylated flavonoid, possesses potent glucose-sensitizing and anti-inflammatory properties; however, its effects in GDM have not been assessed. The present study aimed to determine the effects of nobiletin on glucose metabolism and inflammation associated with GDM in both in vitro human tissues and an in vivo animal model of GDM. In vitro, treatment with nobiletin significantly improved TNF-impaired glucose uptake in human skeletal muscle, and suppressed mRNA expression and protein secretion of pro-inflammatory cytokines and chemokines in human placenta and visceral adipose tissue (VAT). Mechanistically, nobiletin significantly inhibited Akt and Erk activation in placenta, and NF-κB activation in VAT. In vivo, GDM mice treated with 50 mg/kg nobiletin daily via oral gavage from gestational day (gd) 1-17 or via i.p. injections from gd 10-17 significantly improved glucose tolerance. Pregnant GDM mice treated with nobiletin from either gd 1-17 or gd 10-17 exhibited significantly suppressed mRNA expression of pro-inflammatory cytokines and chemokines in placenta, VAT and subcutaneous adipose tissue (SAT). Using a quantitative mass spectrometry approach, we identified differentially abundant proteins associated with the effect of nobiletin in vivo. Together, these studies demonstrate that nobiletin improves glucose metabolism and reduces inflammation associated with GDM and may be a novel therapeutic for the prevention of GDM.

scholarly journals Brain-Derived Neurotropic Factor (BDNF) Mediates the Protective Effect of L.Cucurbita Pepo on Salivary Glands of Depressed Rat Evident by Structural, Biochemical and Molecular Study

2021 ◽  
Author(s):  
Hailah M. ALmohaimeed ◽  
Emad A. Albadawi ◽  
Zuhair M. Mohammedsaleh ◽  
Hadel M. Alghabban ◽  
Hanan S. Seleem ◽  
...  
Keyword(s):  
Salivary Glands ◽  
Inflammatory Cytokines ◽  
Serum Levels ◽  
Albino Rats ◽  
Mild Stress ◽  
Ductal Cells ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
The Impact ◽  
Pro Inflammatory Cytokines

Abstract BackgroundAcute and chronic stresses affect the salivary glands which are the source of plasma BDNF during stressful conditions. Pumpkin is a medicinal plant with an evident antioxidant, anti-inflammatory and potential antidepressant effects. This work was conducted to assess the impact of chronic unpredictable mild stress (CUMS) on the structure of albino rats’ salivary glands and evaluate the role of pumpkin extract (Pump) in ameliorating this effect. MethodsFour groups (n=10 each) of male albino rats included in this study; the control, CUMS, CUMS+fluoxetine and (CUMS+Pump). Corticosterone, pro-inflammatory cytokines (TNF-α & IL-6) and the oxidant/antioxidant profile were all assessed in the serum. BDNF mRNA level was measured in the salivary glands using qRT-PCR. Histopathological changes of the salivary glands were also assessed. ResultsDepression was confirmed behaviorally and biochemically. Exposure to CUMS significantly (p< 0.001) up-regulated the level of serum corticosterone. CUMS induced degenerative changes in the secretory and ductal system, atrophy of acini and increased apoptosis of the acinar and ductal cells. Both fluoxetine and Pump significantly up-regulated (p<0.001) BDNF expression in the salivary glands and ameliorated the CUMS-induced histopathological alterations in the salivary glands. Pumpkin significantly (p<0.001) increased the serum levels of antioxidant enzymes SOD, GPX and CAT and reduced the serum levels of the pro-inflammatory cytokines TNF-α, IL-6.ConclusionPumpkin ameliorates chronic stress-induced depression in rats by exerting a promising anti-inflammatory, antioxidant and anti-depressant-like effects in rats exposed to CUMS. Pump subsequently improved stress-induced structural changes in the salivary glands that might be due to the glands up-regulation of BDNF expression.Trial registrationNot applicable.

scholarly journals Development of an Advanced Multicellular Intestinal Model for Assessing Immunomodulatory Properties of Anti-Inflammatory Compounds

2021 ◽  
Vol 12 ◽  
Author(s):  
Diego Marescotti ◽  
Giuseppe Lo Sasso ◽  
Diego Guerrera ◽  
Kasper Renggli ◽  
Pedro A. Ruiz Castro ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Intestinal Inflammation ◽  
Epithelial Layer ◽  
Barrier Integrity ◽  
Cytokines And Chemokines ◽  
Inflammatory State ◽  
Tobacco Alkaloids ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

Intestinal inflammation is the collective term for immune system-mediated diseases of unknown, multifactorial etiology, with often complex interactions between genetic and environmental factors. To mechanistically investigate the effect of treatment with compounds possessing immunomodulating properties in the context of intestinal inflammation, we developed an immunocompetent in vitro triculture intestinal model consisting of a differentiated intestinal epithelial layer (Caco-2/HT29-MTX) and immunocompetent cells (differentiated THP-1). The triculture mimicked a healthy intestine with stable barrier integrity. Lipopolysaccharide treatment triggered a controlled and reversible inflammatory state, resulting in significant impairment of barrier integrity and release of pro-inflammatory cytokines and chemokines, which are known hallmarks of intestinal inflammation. Treatment with known anti-inflammatory reference compounds (TPCA-1 and budenoside) prevented the induction of an inflammatory state; the decreasing triculture responses to this treatment measured by cytokine release, transepithelial electric resistance (TEER), and epithelial layer permeability proved the suitability of the intestinal model for anti-inflammatory drug screening. Finally, selected tobacco alkaloids (nicotine and anatabine (R/S and S forms)) were tested in the in vitro triculture for their potential anti-inflammatory properties. Indeed, naturally occurring alkaloids, such as tobacco-derived alkaloids, have shown substantial anti-inflammatory effects in several in vitro and in vivo models of inflammation, gaining increasing interest. Similar to the anti-inflammatory reference compounds, one of the tobacco alkaloids under investigation partially prevented the decrease in the TEER and increase in permeability and reduced the release of pro-inflammatory cytokines and chemokines. Taken together, these data confirm that our in vitro model is suitable for screening potential anti-inflammatory compounds in the context of intestinal inflammation.

A Pathophysiological Role for Selective Alteration of the Cytokine-Chemokine Network – Inflammatory Theory in Alzheimer’s Disease

2009 ◽  
Vol 4 (1) ◽  
pp. 22
Author(s):  
Domenico Gambi ◽  
Marcella Reale ◽  
◽  
Keyword(s):  
Inflammatory Cytokines ◽  
Neuronal Damage ◽  
Amyloid Β ◽  
Oxygen Species ◽  
Disease Treatment ◽  
Cytokines And Chemokines ◽  
Pathophysiological Role ◽  
Altered Metabolism ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

There is growing evidence that an altered metabolism of the amyloid β (Aβ) precursor protein (APP) with progressive deposition of its Aβ fragment is a crucial event in the pathogenesis of AD. Increasing evidence suggests that inflammation and alteration of the cytokine–chemokine network contributes to the pathophysiology of AD. Activated microglia produce multiple pro-inflammatory cytokines, chemokines and reactive oxygen species (ROS); additionally, Aβ itself can stimulate microglia, astrocytes and oligodendrocytes to secrete pro-inflammatory cytokines, chemokines and ROS, which can lead to neuronal damage. The concomitant release of pro-inflammatory cytokines, which influence neurodegenerative pathways, and anti-inflammatory cytokines may contribute to the chronicity of the disease. It is the balance of pro-inflammatory products and anti-inflammatory products that may be essential in the degenerative process. Influencing this balance may help in slowing the disease. Promising results for neurological disease treatment may be achieved by targeting cytokines and chemokines in the development of antagonists and synthesis inhibitors.

A Pathophysiological Role for Selective Alteration of the Cytokine–Chemokine Network—Inflammatory Theory in Alzheimer’s Disease

US Neurology ◽  
2009 ◽  
Vol 05 (01) ◽  
pp. 15
Author(s):  
Domenico Gambi ◽  
Marcella Reale ◽  
◽  
Keyword(s):  
Inflammatory Cytokines ◽  
Neuronal Damage ◽  
Amyloid Β ◽  
Oxygen Species ◽  
Disease Treatment ◽  
Cytokines And Chemokines ◽  
Pathophysiological Role ◽  
Altered Metabolism ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

There is growing evidence that an altered metabolism of the amyloid β (Aβ) precursor protein (APP) with progressive deposition of its Aβ fragment is a crucial event in the pathogenesis of AD. Increasing evidence suggests that inflammation and alteration of the cytokine–chemokine network contributes to the pathophysiology of AD. Activated microglia produce multiple pro-inflammatory cytokines, chemokines, and reactive oxygen species (ROS); additionally, Aβ itself can stimulate microglia, astrocytes, and oligodendrocytes to secrete pro-inflammatory cytokines, chemokines, and ROS, which can lead to neuronal damage. The concomitant release of pro-inflammatory cytokines, which influence neurodegenerative pathways, and anti-inflammatory cytokines may contribute to the chronicity of the disease. It is the balance of proinflammatory products and anti-inflammatory products that may be essential in the degenerative process. Influencing this balance may help in slowing the disease. Promising results for neurological disease treatment may be achieved by targeting cytokines and chemokines in the development of antagonists and synthesis inhibitors.

Pro- and anti-inflammatory response profile modulates Plasmodium falciparum malaria outcomes among subjects from Baiyeku, Ikorodu, Lagos, Nigeria.

2020 ◽  
Author(s):  
Daniel Osegi Okpokor ◽  
Olusola Ajibaye ◽  
Peter Mac Asaga ◽  
Ikechukwu Nwankwo ◽  
Anthony Danaan Dakul
Keyword(s):  
Plasmodium Falciparum ◽  
Inflammatory Cytokines ◽  
Parasite Density ◽  
World Health ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tnf Α ◽  
Significant Difference ◽  
Ifn Γ ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

Abstract Background Available evidence indicates that the various stages of the malaria parasite life cycle elicit specific immune responses of which the relative levels of pro-inflammatory cytokines are key to disease progression, killing the parasite and mediating disease outcomes. This study will inform immunological interventions against malaria and thus malaria vaccine developments programs/efforts. Methods A total of four hundred and sixty-two participants were screened in a community survey for Plasmodium falciparum (P. falciparum) malaria in Baiyeku, Lagos, Nigeria. P. falciparum parasitaemia was determined by Microscopy using thick and thin blood films stained by Giemsa method using World Health Organization parasitology laboratory protocol whist the serum levels of IL-10, IFNγ and TNFα were determined by Enzyme linked immunosorbent assay [ELISA]. Data analysis was done by One-way Analysis of Variance (ANOVA), Chi square (X²) and Student’s T-test in statistical package for the social sciences (SPSS) version 24 was used to test statistical significance between the symptomatic groups and asymptomatic in relation to age, gender and BMI of the participants.Results A total of 70 (15.2 %) participants were microscopically positive for P. falciparum of which 70% were female, 30% were males while children aged 1-17 years were 65.7%. The geometric mean parasite density (GMPD) was significantly (p=0.001) higher among females than males. The GMPD of participants < 5 years was also significantly (p=0.001) higher than other age groups. About 46.8% of the participants were underweight (BMI < 18.5) also had the highest parasite intensity. The TNFα, IFNγ and IL-10 levels were significantly (p 0.05) higher in the infected than the uninfected participants. IFN-γ values were significantly (p=0.014) elevated among the symptomatic than the asymptomatic participants while there was no significant difference (P>0.053) in the levels of TNF-α and IL-10 (P>0.093) between the symptomatic and asymptomatic participants. Notably, the IL-10 levels were the most elevated amongst the participants with the highest parasite density.Conclusion The prevalence of P. falciparum obtained in this study area which is endemic for malaria is 15.2% suggesting a significant reduction of the disease over time. The awareness of the disease which is now more than before seems to contribute to the lowering of prevalence of the disease in the community. There was a positive relationship between TNF-alpha levels and body temperature. However, compared with the anti-inflammatory cytokine (IL-10) in this study, the levels of the pro-inflammatory cytokines (IFN-γ and TNF-α) were lower due to the negative action of the anti-inflammatory cytokines. IL-10 value increased as parasitemia increased (p=0.073). These findings suggest that higher levels of anti-inflammatory cytokines, especially IL-10 levels may contribute to pathogenesis of uncomplicated malaria.

scholarly journals Transcryptomic Analysis of Human Brain Microvascular Endothelial Response to-Pericytes: Cell Orientation Defines Barrier Function

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 963
Author(s):  
Lisa Kurmann ◽  
Michal Okoniewski ◽  
Omolara O. Ogunshola ◽  
Brigitte Leeners ◽  
Bruno Imthurn ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Barrier Function ◽  
Drug Transport ◽  
Transforming Growth Factor ◽  
Receptor Interaction ◽  
Pathway Enrichment Analysis ◽  
Cytokines And Chemokines ◽  
Microvascular Endothelial ◽  
The Impact ◽  
Pro Inflammatory Cytokines

Pericytes facilitate blood–brain barrier (BBB) integrity; however, the mechanisms involved remain unclear. Hence, using co-cultures of human cerebral microvascular endothelial cells (ECs) and vascular pericytes (PCs) in different spatial arrangements, as well as PC conditioned media, we investigated the impact of PC-EC orientation and PC-derived soluble factors on EC barrier function. We provide the first evidence that barrier-inducing properties of PCs require basolateral contact with ECs. Gene expression analysis (GEA) in ECs co-cultured with PCs versus ECs alone showed significant upregulation of 38 genes and downregulation of 122 genes. Pathway enrichment analysis of modulated genes showed significant regulation of several pathways, including transforming growth factor-β and interleukin-1 regulated extracellular matrix, interferon and interleukin signaling, immune system signaling, receptor of advanced glycation end products (RAGE), and cytokine–cytokine receptor interaction. Transcriptomic analysis showed a reduction in molecules such as pro-inflammatory cytokines and chemokines, which are known to be induced during BBB disruption. Moreover, cytokine proteome array confirmed the downregulation of key pro-inflammatory cytokines and chemokines on the protein level. Other molecules which influence BBB and were favorably modulated upon EC-PC co-culture include IL-18 binding protein, kallikrein-3, CSF2 CSF3, CXCL10, CXCL11 (downregulated) and IL-1-R4; HGF, PDGF-AB/BB, PECAM, SERPIN E1 (upregulated). In conclusion, we provide the first evidence that (1) basolateral contact between ECs and PCs is essential for EC barrier function and integrity; (2) in ECs co-cultured with PCs, the profile of BBB disrupting pro-inflammatory molecules and cytokines/chemokines is downregulated; (3) PCs significantly modulate EC mechanisms known to improve barrier function, including TGF-β regulated ECM pathway, anti-inflammatory cytokines, growth factors and matrix proteins. This human PC-EC co-culture may serve as a viable in vitro model for investigating BBB function and drug transport.

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