scholarly journals n-3 Fatty acids, inflammation and immunity: new mechanisms to explain old actions

2013 ◽  
Vol 72 (3) ◽  
pp. 326-336 ◽  
Author(s):  
Philip C. Calder
Keyword(s):  
Fatty Acids ◽  
Inflammatory Responses ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Mechanisms Of Action ◽  
Lipid Mediators ◽  
Functional Responses ◽  
New Family ◽  
Epa And Dha ◽  
Novel Interactions

Numerous effects of n-3 fatty acids EPA and DHA on functional responses of cells involved in inflammation and immunity have been described. Fatty acid-induced modifications in membrane order and in the availability of substrates for eicosanoid synthesis are long-standing mechanisms that are considered important in explaining the effects observed. More recently, effects on signal transduction pathways and on gene expression profiles have been identified. Over the last 10 years or so, significant advances in understanding the mechanisms of action of n-3 fatty acids have been made. These include the identification of new actions of lipid mediators that were already described and of novel interactions among those mediators and the description of an entirely new family of lipid mediators, resolvins and protectins that have anti-inflammatory actions and are critical to the resolution of inflammation. It is also recognised that EPA and DHA can inhibit activation of the prototypical inflammatory transcription factor NF-κB. Recent studies suggest three alternative mechanisms by which n-3 fatty acids might have this effect. Within T-cells, as well as other cells of relevance to immune and inflammatory responses, EPA and DHA act to disrupt very early events involving formation of the structures termed lipid rafts which bring together various proteins to form an effective signalling platform. In summary, recent research has identified a number of new mechanisms of action that help to explain previously identified effects of n-3 fatty acids on inflammation and immunity.

Whole blood genome-wide gene expression profile in males after prolonged wakefulness and sleep recovery

2012 ◽  
Vol 44 (21) ◽  
pp. 1003-1012 ◽  
Author(s):  
R. Pellegrino ◽  
D. Y. Sunaga ◽  
C. Guindalini ◽  
R. C. S. Martins ◽  
D. R. Mazzotti ◽  
...  
Keyword(s):  
Gene Expression ◽  
Whole Blood ◽  
Inflammatory Responses ◽  
Expression Profiles ◽  
Killer Cell ◽  
Gene Expression Profiles ◽  
Sleep Loss ◽  
The Body ◽  
Dna Damage And Repair ◽  
Peripheral Tissues

Although the specific functions of sleep have not been completely elucidated, the literature has suggested that sleep is essential for proper homeostasis. Sleep loss is associated with changes in behavioral, neurochemical, cellular, and metabolic function as well as impaired immune response. Using high-resolution microarrays we evaluated the gene expression profiles of healthy male volunteers who underwent 60 h of prolonged wakefulness (PW) followed by 12 h of sleep recovery (SR). Peripheral whole blood was collected at 8 am in the morning before the initiation of PW (Baseline), after the second night of PW, and one night after SR. We identified over 500 genes that were differentially expressed. Notably, these genes were related to DNA damage and repair and stress response, as well as diverse immune system responses, such as natural killer pathways including killer cell lectin-like receptors family, as well as granzymes and T-cell receptors, which play important roles in host defense. These results support the idea that sleep loss can lead to alterations in molecular processes that result in perturbation of cellular immunity, induction of inflammatory responses, and homeostatic imbalance. Moreover, expression of multiple genes was downregulated following PW and upregulated after SR compared with PW, suggesting an attempt of the body to re-establish internal homeostasis. In silico validation of alterations in the expression of CETN3, DNAJC, and CEACAM genes confirmed previous findings related to the molecular effects of sleep deprivation. Thus, the present findings confirm that the effects of sleep loss are not restricted to the brain and can occur intensely in peripheral tissues.

scholarly journals Regulation of Cellular Metabolism and Cytokines by the Medicinal Herb Feverfew in the Human Monocytic THP-1 Cells

2009 ◽  
Vol 6 (1) ◽  
pp. 91-98 ◽  
Author(s):  
Chin-Fu Chen ◽  
Chun-Huai Cheng
Keyword(s):  
Cytokine Production ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Cellular Metabolism ◽  
Mechanisms Of Action ◽  
Human Monocytes ◽  
Cellular Targets ◽  
Tnf Α ◽  
Folk Remedy ◽  
Mediate Metabolism

The herb feverfew is a folk remedy for various symptoms including inflammation. Inflammation has recently been implicated in the genesis of many diseases including cancers, atherosclerosis and rheumatoid arthritis. The mechanisms of action of feverfew in the human body are largely unknown. To determine the cellular targets of feverfew extracts, we have utilized oligo microarrays to study the gene expression profiles elicited by feverfew extracts in human monocytic THP-1 cells. We have identified 400 genes that are consistently regulated by feverfew extracts. Most of the genes are involved in cellular metabolism. However, the genes undergoing the highest degree of change by feverfew treatment are involved in other pathways including chemokine function, water homeostasis and heme-mediated signaling. Our results also suggest that feverfew extracts effectively reduce Lipopolysaccharides (LPS)-mediated TNF-α and CCL2 (MCP-1) releases by THP-1 cells. We hypothesize that feverfew components mediate metabolism, cell migration and cytokine production in human monocytes/macrophages.

scholarly journals Diversity of caecal bacteria is altered in interleukin-10 gene-deficient mice before and after colitis onset and when fed polyunsaturated fatty acids

Microbiology ◽  
2010 ◽  
Vol 156 (11) ◽  
pp. 3306-3316 ◽  
Author(s):  
Bianca Knoch ◽  
Katia Nones ◽  
Matthew P. G. Barnett ◽  
Warren C. McNabb ◽  
Nicole C. Roy
Keyword(s):  
Fatty Acids ◽  
Bacterial Community ◽  
Polyunsaturated Fatty Acids ◽  
Expression Profiles ◽  
Clinical Signs ◽  
Gene Expression Profiles ◽  
Intestinal Bacteria ◽  
Interleukin 10 ◽  
Dietary Pufa ◽  
Pufa Supplementation

Interleukin-10 gene-deficient (Il10 –/–) mice show a hyper-reaction to normal intestinal bacteria and develop spontaneous colitis similar to that of human Crohn's disease when raised under conventional (but not germ-free) conditions. The lack of IL10 protein in these mice leads to changes in intestinal metabolic and signalling processes. The first aim of this study was to identify changes in the bacterial community of the caeca at 7 weeks of age (preclinical colitis) and at 12 weeks of age (when clinical signs of colitis are present), and establish if there were any changes that could be associated with the mouse genotype. We have previously shown that dietary n-3 and n-6 polyunsaturated fatty acids (PUFA) have anti-inflammatory effects and affect colonic gene expression profiles in Il10 –/– mice; therefore, we also aimed to test the effect of the n-3 PUFA eicosapentaenoic acid (EPA) and the n-6 PUFA arachidonic acid (AA) on the bacterial community of caeca in both Il10 –/– and C57 mice fed these diets. The lower number of caecal bacteria observed before colitis (7 weeks of age) in Il10 –/– compared to C57 mice suggests differences in the intestinal bacteria that might be associated with the genotype, and this could contribute to the development of colitis in this mouse model. The number and diversity of caecal bacteria increased after the onset of colitis (12 weeks of age). The increase in caecal Escherichia coli numbers in both inflamed Il10 –/– and healthy C57 mice might be attributed to the dietary PUFA (especially dietary AA), and thus not be a cause of colitis development. A possible protective effect of E. coli mediated by PUFA supplementation and associated changes in the bacterial environment could be a subject for further investigation to define the mode of action of PUFA in colitis.

Distinct gene expression profiles provoked by polyacrylamide beads (Biogel) during chronic and acute inflammation in mice selected for maximal and minimal inflammatory responses

2016 ◽  
Vol 65 (4) ◽  
pp. 313-323 ◽  
Author(s):  
Jussara Gonçalves Fernandes ◽  
Tatiane Canhamero ◽  
Andrea Borrego ◽  
José Ricardo Jensen ◽  
Wafa Hanna Cabrera ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Inflammation ◽  
Inflammatory Responses ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Distinct Gene

scholarly journals MR Imaging Distinguishes Tumor Hypoxia Levels of Different Prognostic and Biological Significance in Cervical Cancer

2020 ◽  
Author(s):  
Tiril Hillestad ◽  
Tord Hompland ◽  
Christina S. Fjeldbo ◽  
Vilde E. Skingen ◽  
Unn Beate Salberg ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Epithelial To Mesenchymal Transition ◽  
Inflammatory Responses ◽  
Expression Profiles ◽  
Tumor Hypoxia ◽  
Biological Significance ◽  
Gene Expression Profiles ◽  
Interferon Response ◽  
Moderate Hypoxia ◽  
Mesenchymal Transition

AbstractTumor hypoxia levels range from mild to severe and have different biological and therapeutical consequences, but are not easily assessable in patients. We present a method based on diagnostic dynamic contrast enhanced (DCE) magnetic resonance imaging (MRI) that visualizes a continuous range of hypoxia levels in tumors of cervical cancer patients. Hypoxia images were generated using an established approach based on pixel-wise combination of the DCE-MRI parameters νe and Ktrans, reflecting oxygen consumption and supply, respectively. An algorithm to retrieve hypoxia levels from the images was developed and validated in 28 xenograft tumors, by comparing the MRI-defined levels with hypoxia levels derived from pimonidazole stained histological sections. We further established an indicator of hypoxia levels in patient tumors based on expression of nine hypoxia responsive genes. A strong correlation was found between these indicator values and the MRI-defined hypoxia levels in 63 patients. Chemoradiotherapy outcome of 74 patients was most strongly predicted by moderate hypoxia levels, whereas more severe or milder levels were less predictive. By combining gene expression profiles and MRI-defined hypoxia levels in cancer hallmark analysis, we identified a distribution of levels associated with each hallmark; oxidative phosphorylation and G2/M checkpoint were associated with moderate hypoxia, and epithelial-to-mesenchymal transition and inflammatory responses with significantly more severe levels. At the mildest levels, interferon response hallmarks, together with stabilization of HIF1A protein by immunohistochemistry, appearred significant. Thus, our method visualizes the distribution of hypoxia levels within patient tumors and has potential to distinguish levels of different prognostic and biological significance.

scholarly journals Prion Infection of Mouse Brain Reveals Multiple New Upregulated Genes Involved in Neuroinflammation or Signal Transduction

2014 ◽  
Vol 89 (4) ◽  
pp. 2388-2404 ◽  
Author(s):  
James A. Carroll ◽  
James F. Striebel ◽  
Brent Race ◽  
Katie Phillips ◽  
Bruce Chesebro
Keyword(s):  
Signal Transduction ◽  
Inflammatory Responses ◽  
Prion Diseases ◽  
Expression Profiles ◽  
Signal Transduction Pathway ◽  
Gene Expression Profiles ◽  
Observable Effect ◽  
Prion Infection ◽  
Scrapie Infection ◽  
Scrapie Strains

ABSTRACTGliosis is often a preclinical pathological finding in neurodegenerative diseases, including prion diseases, but the mechanisms facilitating gliosis and neuronal damage in these diseases are not understood. To expand our knowledge of the neuroinflammatory response in prion diseases, we assessed the expression of key genes and proteins involved in the inflammatory response and signal transduction in mouse brain at various times after scrapie infection. In brains of scrapie-infected mice at pre- and postclinical stages, we identified 15 previously unreported differentially expressed genes related to inflammation or activation of the STAT signal transduction pathway. Levels for the majority of differentially expressed genes increased with time postinfection. In quantitative immunoblotting experiments of STAT proteins, STAT1α, phosphorylated-STAT1α (pSTAT1α), and pSTAT3 were increased between 94 and 131 days postinfection (p.i.) in brains of mice infected with strain 22L. Furthermore, a select group of STAT-associated genes was increased preclinically during scrapie infection, suggesting early activation of the STAT signal transduction pathway. Comparison of inflammatory markers between mice infected with scrapie strains 22L and RML indicated that the inflammatory responses and gene expression profiles in the brains were strikingly similar, even though these scrapie strains infect different brain regions. The endogenous interleukin-1 receptor antagonist (IL-1Ra), an inflammatory marker, was newly identified as increasing preclinically in our model and therefore might influence scrapie pathogenesisin vivo. However, in IL-1Ra-deficient or overexpressor transgenic mice inoculated with scrapie, neither loss nor overexpression of IL-1Ra demonstrated any observable effect on gliosis, protease-resistant prion protein (PrPres) formation, disease tempo, pathology, or expression of the inflammatory genes analyzed.IMPORTANCEPrion infection leads to PrPres deposition, gliosis, and neuroinflammation in the central nervous system before signs of clinical illness. Using a scrapie mouse model of prion disease to assess various time points postinoculation, we identified 15 unreported genes that were increased in the brains of scrapie-infected mice and were associated with inflammation and/or JAK-STAT activation. Comparison of mice infected with two scrapie strains (22L and RML), which have dissimilar neuropathologies, indicated that the inflammatory responses and gene expression profiles in the brains were similar. Genes that increased prior to clinical signs might be involved in controlling scrapie infection or in facilitating damage to host tissues. We tested the possible role of the endogenous IL-1Ra, which was increased at 70 days p.i. In scrapie-infected mice deficient in or overexpressing IL-1Ra, there was no observable effect on gliosis, PrPres formation, disease tempo, pathology, or expression of inflammatory genes analyzed.

scholarly journals Attenuated Rabies Virus Activates, while Pathogenic Rabies Virus Evades, the Host Innate Immune Responses in the Central Nervous System

2005 ◽  
Vol 79 (19) ◽  
pp. 12554-12565 ◽  
Author(s):  
Zhi W. Wang ◽  
Luciana Sarmento ◽  
Yuhuan Wang ◽  
Xia-qing Li ◽  
Vikas Dhingra ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Rabies Virus ◽  
Inflammatory Responses ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Innate Immune ◽  
Host Responses ◽  
Oligoadenylate Synthetase ◽  
Antiviral Responses ◽  
Inflammatory Chemokines

ABSTRACT Rabies virus (RV) induces encephalomyelitis in humans and animals. However, the pathogenic mechanism of rabies is not fully understood. To investigate the host responses to RV infection, we examined and compared the pathology, particularly the inflammatory responses, and the gene expression profiles in the brains of mice infected with wild-type (wt) virus silver-haired bat RV (SHBRV) or laboratory-adapted virus B2C, using a mouse genomic array (Affymetrix). Extensive inflammatory responses were observed in animals infected with the attenuated RV, but little or no inflammatory responses were found in mice infected with wt RV. Furthermore, attenuated RV induced the expression of the genes involved in the innate immune and antiviral responses, especially those related to the alpha/beta interferon (IFN-α/β) signaling pathways and inflammatory chemokines. For the IFN-α/β signaling pathways, many of the interferon regulatory genes, such as the signal transduction activation transducers and interferon regulatory factors, as well as the effector genes, for example, 2′-5′-oligoadenylate synthetase and myxovirus proteins, are highly induced in mice infected with attenuated RV. However, many of these genes were not up-regulated in mice infected with wt SHBRV. The data obtained by microarray analysis were confirmed by real-time PCR. Together, these data suggest that attenuated RV activates, while pathogenic RV evades, the host innate immune and antiviral responses.

scholarly journals Glabralysins, Potential New β-Pore-Forming Toxin Family Members from the Schistosomiasis Vector Snail Biomphalaria glabrata

Genes ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 65
Author(s):  
Damien Lassalle ◽  
Guillaume Tetreau ◽  
Silvain Pinaud ◽  
Richard Galinier ◽  
Neil Crickmore ◽  
...  
Keyword(s):  
Structure Prediction ◽  
Tertiary Structure ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Biomphalaria Glabrata ◽  
Amino Acid Identity ◽  
New Family ◽  
New Genes ◽  
High Degree ◽  
Trematode Parasites

Biomphalaria glabrata is a freshwater Planorbidae snail. In its environment, this mollusk faces numerous microorganisms or pathogens, and has developed sophisticated innate immune mechanisms to survive. The mechanisms of recognition are quite well understood in Biomphalaria glabrata, but immune effectors have been seldom described. In this study, we analyzed a new family of potential immune effectors and characterized five new genes that were named Glabralysins. The five Glabralysin genes showed different genomic structures and the high degree of amino acid identity between the Glabralysins, and the presence of the conserved ETX/MTX2 domain, support the hypothesis that they are pore-forming toxins. In addition, tertiary structure prediction confirms that they are structurally related to a subset of Cry toxins from Bacillus thuringiensis, including Cry23, Cry45, and Cry51. Finally, we investigated their gene expression profiles in snail tissues and demonstrated a mosaic transcription. We highlight the specificity in Glabralysin expression following immune stimulation with bacteria, yeast or trematode parasites. Interestingly, one Glabralysin was found to be expressed in immune-specialized hemocytes, and two others were induced following parasite exposure.

scholarly journals Gene expression profiling of the effects of organic dust in lung epithelial and THP-1 cells reveals inductive effects on inflammatory and immune response genes

2016 ◽  
Vol 48 (4) ◽  
pp. 281-289 ◽  
Author(s):  
Vijay Boggaram ◽  
David S. Loose ◽  
Koteswara R. Gottipati ◽  
Kartiga Natarajan ◽  
Courtney T. Mitchell
Keyword(s):  
Gene Expression ◽  
Inflammatory Responses ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Organic Dust ◽  
Monocytic Cells ◽  
Lung Epithelial ◽  
Poultry Dust ◽  
Induced Changes ◽  
Dust Extract

The intensification and concentration of animal production operations expose workers to high levels of organic dusts in the work environment. Exposure to organic dusts is a risk factor for the development of acute and chronic respiratory symptoms and diseases. Lung epithelium plays important roles in the control of immune and inflammatory responses to environmental agents to maintain lung health. To better understand the effects of organic dust on lung inflammatory responses, we characterized the gene expression profiles of A549 alveolar and Beas2B bronchial epithelial and THP-1 monocytic cells influenced by exposure to poultry dust extract by DNA microarray analysis using Illumina Human HT-12 v4 Expression BeadChip. We found that A549 alveolar and Beas2B bronchial epithelial and THP-1 cells responded with unique changes in the gene expression profiles with regulation of genes encoding inflammatory cytokines, chemokines, and other inflammatory proteins being common to all the three cells. Significantly induced genes included IL-8, IL-6, IL-1β, ICAM-1, CCL2, CCL5, TLR4, and PTGS2. Validation by real-time qRT-PCR, ELISA, Western immunoblotting, and immunohistochemical staining of lung sections from mice exposed to dust extract validated DNA microarray results. Pathway analysis indicated that dust extract induced changes in gene expression influenced functions related to cellular growth and proliferation, cell death and survival, and cellular development. These data show that a broad range of inflammatory mediators produced in response to poultry dust exposure can modulate lung immune and inflammatory responses. This is the first report on organic dust induced changes in expression profiles in lung epithelial and THP-1 monocytic cells.

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