Trans Fatty Acids Suppress TNF-α-Induced Inflammatory Gene Expression in Endothelial (HUVEC) and Hepatocellular Carcinoma (HepG2) Cells

Lipids ◽  
2017 ◽  
Vol 52 (4) ◽  
pp. 315-325 ◽  
Author(s):  
Marine S. Da Silva ◽  
Pierre Julien ◽  
Jean-François Bilodeau ◽  
Olivier Barbier ◽  
Iwona Rudkowska
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Fatty Acids ◽  
Hepg2 Cells ◽  
Trans Fatty Acids ◽  
Inflammatory Gene Expression ◽  
Inflammatory Gene ◽  
Tnf Α

scholarly journals The effects of n-6 polyunsaturated fatty acid deprivation on the inflammatory gene response to lipopolysaccharide in the mouse hippocampus

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Shoug M. Alashmali ◽  
Lin Lin ◽  
Marc-Olivier Trépanier ◽  
Giulia Cisbani ◽  
Richard P. Bazinet
Keyword(s):  
Gene Expression ◽  
Fatty Acids ◽  
Diet Group ◽  
Inflammatory Gene Expression ◽  
Inflammatory Gene ◽  
Left Lateral Ventricle ◽  
Gene Response ◽  
Mouse Hippocampus ◽  
Total Fatty Acids ◽  
The Brain

Abstract Background Neuroinflammation is thought to contribute to psychiatric and neurological disorders such as major depression and Alzheimer’s disease (AD). N-6 polyunsaturated fatty acids (PUFA) and molecules derived from them, including linoleic acid- and arachidonic acid-derived lipid mediators, are known to have pro-inflammatory properties in the periphery; however, this has yet to be tested in the brain. Lowering the consumption of n-6 PUFA is associated with a decreased risk of depression and AD in human observational studies. The purpose of this study was to investigate the inflammation-modulating effects of lowering dietary n-6 PUFA in the mouse hippocampus. Methods C57BL/6 male mice were fed either an n-6 PUFA deprived (2% of total fatty acids) or an n-6 PUFA adequate (23% of total fatty acids) diet from weaning to 12 weeks of age. Animals then underwent intracerebroventricular surgery, in which lipopolysaccharide (LPS) was injected into the left lateral ventricle of the brain. Hippocampi were collected at baseline and following LPS administration (1, 3, 7, and 14 days). A microarray (n = 3 per group) was used to identify candidate genes and results were validated by real-time PCR in a separate cohort of animals (n = 5–8 per group). Results Mice administered with LPS had significantly increased Gene Ontology categories associated with inflammation and immune responses. These effects were independent of changes in gene expression in any diet group. Results were validated for the effect of LPS treatment on astrocyte, cytokine, and chemokine markers, as well as some results of the diets on Ifrd2 and Mfsd2a expression. Conclusions LPS administration increases pro-inflammatory and lipid-metabolizing gene expression in the mouse hippocampus. An n-6 PUFA deprived diet modulated inflammatory gene expression by both increasing and decreasing inflammatory gene expression, without impairing the resolution of neuroinflammation following LPS administration.

scholarly journals Effect of Free Fatty Acids on Inflammatory Gene Expression and Hydrogen Peroxide Production by Ex Vivo Blood Mononuclear Cells

Nutrients ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 146 ◽  
Author(s):  
Antoni Sureda ◽  
Miquel Martorell ◽  
Maria del Mar Bibiloni ◽  
Cristina Bouzas ◽  
Laura Gallardo-Alfaro ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fatty Acids ◽  
Free Fatty Acids ◽  
Mononuclear Cells ◽  
Ex Vivo ◽  
H2o2 Production ◽  
Inflammatory Gene Expression ◽  
Inflammatory Gene ◽  
Blood Mononuclear Cells ◽  
Docosahexaenoic Acids

The aim of this study was to assess free fatty acids’ (FAs) ex vivo anti-/proinflammatory capabilities and their influence on inflammatory gene expression and H2O2 production by human peripheral blood mononuclear cells (PBMCs). Anthropometric and clinical measurements were performed in 26 participants with metabolic syndrome. Isolated PBMCs were incubated ex vivo for 2 h with several free fatty acids—palmitic, oleic, α-linolenic, γ-linolenic, arachidonic and docosahexaenoic at 50 μM, and lipopolysaccharide (LPS) alone or in combination. H2O2 production and IL6, NFκB, TLR2, TNFα, and COX-2 gene expressions were determined. Palmitic, γ-linolenic, and arachidonic acids showed minor effects on inflammatory gene expression, whereas oleic, α-linolenic, and docosahexaenoic acids reduced proinflammatory gene expression in LPS-stimulated PBMCs. Arachidonic and α-linolenic acids treatment enhanced LPS-stimulated H2O2 production by PBMCs, while palmitic, oleic, γ-linolenic, and docosahexaenoic acids did not exert significant effects. Oleic, α-linolenic, and docosahexaenoic acids induced anti-inflammatory responses in PBMCs. Arachidonic and α-linolenic acids enhanced the oxidative status of LPS-stimulated PBMCs. In conclusion, PBMC ex vivo assays are useful to assess the anti-/proinflammatory and redox-modulatory effects of fatty acids or other food bioactive compounds.

Activation of Nrf2/ARE pathway protects endothelial cells from oxidant injury and inhibits inflammatory gene expression

2006 ◽  
Vol 290 (5) ◽  
pp. H1862-H1870 ◽  
Author(s):  
Xi-Lin Chen ◽  
Geraldine Dodd ◽  
Suzanne Thomas ◽  
Xiaolan Zhang ◽  
Martin A. Wasserman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Map Kinase ◽  
P38 Map Kinase ◽  
Control Element ◽  
Related Factor ◽  
Dependent Manner ◽  
Inflammatory Gene Expression ◽  
Inflammatory Gene ◽  
Tnf Α

The antioxidant response element (ARE) is a transcriptional control element that mediates expression of a set of antioxidant proteins. NF-E2-related factor 2 (Nrf2) is a transcription factor that activates ARE-containing genes. In endothelial cells, the ARE-mediated genes are upregulated by atheroprotective laminar flow through a Nrf2-dependent mechanism. We tested the hypothesis that activation of ARE-regulated genes via adenovirus-mediated expression of Nrf2 may suppress redox-sensitive inflammatory gene expression. Expression of Nrf2 in human aortic endothelial cells (HAECs) resulted in a marked increase in ARE-driven transcriptional activity and protected HAECs from H2O2-mediated cytotoxicity. Nrf2 suppressed TNF-α-induced monocyte chemoattractant protein (MCP)-1 and VCAM-1 mRNA and protein expression in a dose-dependent manner and inhibited TNF-α-induced monocytic U937 cell adhesion to HAECs. Nrf2 also inhibited IL-1β-induced MCP-1 gene expression in human mesangial cells. Expression of Nrf2 inhibited TNF-α-induced activation of p38 MAP kinase. Furthermore, expression of a constitutively active form of MKK6 (an upstream kinase for p38 MAP kinase) partially reversed Nrf2-mediated inhibition of VCAM-1 expression, suggesting that p38 MAP kinase, at least in part, mediates Nrf2's anti-inflammatory action. In contrast, Nrf2 did not inhibit TNF-α-induced NF-κB activation. These data identify the Nrf2/ARE pathway as an endogenous atheroprotective system for antioxidant protection and suppression of redox-sensitive inflammatory genes, suggesting that targeting the Nrf2/ARE pathway may represent a novel therapeutic approach for the treatment of inflammatory diseases such as atherosclerosis.

Bile acid signaling through FXR induces intracellular adhesion molecule-1 expression in mouse liver and human hepatocytes

2005 ◽  
Vol 289 (2) ◽  
pp. G267-G273 ◽  
Author(s):  
Pu Qin ◽  
Lisa A. Borges-Marcucci ◽  
Mark J. Evans ◽  
Douglas C. Harnish
Keyword(s):  
Gene Expression ◽  
Bile Acid ◽  
Human Hepatocytes ◽  
Mrna Levels ◽  
Response Element ◽  
Inflammatory Gene Expression ◽  
Inflammatory Gene ◽  
Selective Agonist ◽  
Tnf Α ◽  
Dose Dependent

Previous studies have demonstrated a dramatic induction of inflammatory gene expression in livers from mice fed a high-fat, high-cholesterol diet containing cholate after 3–5 wk. To determine the contribution of cholate in mediating these inductions, C57BL/6 mice were fed a chow diet supplemented with increasing concentrations of cholic acid (CA) for 5 days. A dose-dependent induction in the hepatic levels of TNF-α, VCAM-1, ICAM-1, and SAA-2 mRNA were observed. As positive controls, a dose-dependent repression of cholesterol 7α-hydroxylase and a dose-dependent induction of small heterodimer partner (SHP) expression were also observed, suggesting that farnesoid X receptor (FXR) was activated. In addition, ICAM-1 and SHP mRNA levels were also induced in primary human hepatocytes when treated with chenodeoxycholic acid or GW4064, a FXR-selective agonist. The involvement of FXR in CA-induced inflammatory gene expression was further investigated in the human hepatic cell line HepG2. Both ICAM-1 and SHP expression were induced in a dose- and time- dependent manner by treatment with the FXR-selective agonist GW4064. Moreover, the induction of ICAM-1 by GW4064 was inhibited by the FXR antagonist guggulsterone or with transfection of FXR siRNA. Finally, the activity of FXR was mapped to a retinoic acid response element (RARE) site containing an imbedded farnesoid X response element (FXRE) on the human ICAM-1 promoter and FXR and retinoid X receptor were demonstrated to bind to this site. Finally, FXR-mediated activation of ICAM-1 could be further enhanced by TNF-α cotreatment in hepatocytes, suggesting a potential cooperation between cytokine and bile acid-signaling pathways during hepatic inflammatory events.

scholarly journals Hemolysis Controls Pro-Inflammatory Monocyte Priming Via Induction of and Interaction with Circadian Clock Protein Rev-Erbα in Sickle Cell Disease

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3396-3396
Author(s):  
Julia Brittain ◽  
Itia Lee ◽  
Ciprian Anea
Keyword(s):  
Gene Expression ◽  
Inflammatory Response ◽  
Circadian Clock ◽  
Inflammatory Cytokines ◽  
Low Dose ◽  
Inflammatory Gene Expression ◽  
Inflammatory Gene ◽  
Tnf Α ◽  
Clock Protein

Abstract Background: Patients with SCD tolerate a systemic pro-inflammatory vascular milieu created by chronic ischemia/reperfusion injury and profound erythrocyte hemolysis. In addition to this chronic low level inflammation, exposure to relatively innocuous, sub-clinical inflammatory stimuli appears to ignite an exaggerated, potentially fatal inflammatory response in patients. The etiology of this inflammatory hyper-reactivity is not well understood. There is ample evidence that, in steady state, a cadre of inflammatory cells, especially monocytes, exhibit a primed phenotype. Such priming, or propensity to activate, likely contributes to baseline inflammation, and is requisite for the inflated inflammatory response. Monocytes are quite unique amongst the leukocytes in that their inflammatory potential, including Il-6 release, is governed by the mammalian circadian clock. A role for the rhythmic oscillation of clock proteins as a controller of inflammation in SCD has never been demonstrated. However, a binding partner for heme, the nuclear receptor rev-erbα, is implicated as a regulator of clock controlled genes. Objective: To test the hypothesis that hemolysis, via heme-induced perturbation of the clock protein Rev-erbα, forms the basis for an enhanced inflammatory response in the monocyte. Methods: Intraperitoneal low dose lipopolysaccharide (LPS) was used to elicit an inflammatory response in the Townes mouse model of SCD. Plasma from the mice was acquired 6 hours after LPS injection. Analysis of 25 cytokines was accomplished using luminex methods. Monocytes were modeled in vitro using THP-1 cells. Simultaneous analysis of 84 induced inflammatory genes was conducted via qRT-PCR using the Qiagen RT Profiler PCR array. Inflammatory cytokine levels in cell supernatants were determined via ELISA. Results: We challenged the mice with low dose LPS (<10ng). Interrogation of the inflammatory cytokines in these mice revealed no change in any cytokine tested in the AA mice, but 20 out of 25 inflammatory cytokines were upregulated in mice with the SS genotype. The monocyte-based cytokines were clearly target of LPS activation in the SS mice. TNF-α and Il-1β were both upregulated 20 fold and 80 fold respectively in the SS mice. KC levels (the murine equivalent of Il-8) levels were increased 80 fold in the SS mice treated with LPS. Il-6 levels, however, were the most pronounced with a 40,000 fold increase over PBS injected SS mice. We then evaluated the role of hemolysis on monocyte inflammatory potential in vitro. Sustained monocyte exposure to physiological levels of heme in SCD alone could induce a low level of inflammatory gene expression and Il-6 release. However, sustained exposure to heme dramatically increased Il-6 release from the monocyte in response to LPS. Expression of the Il-6 gene was also increased, but the peak gene expression was time delayed compared to LPS treatment alone. In fact, we noted this phase shifting of inflammatory gene expression in the heme primed cells. LPS induced the release of significantly more TNF-α and Il-1β into the culture media in the presence of heme - consistent with the notion of heme setting a hyperactive threshold in response to LPS. We also noted that heme induced expression of the clock gene rev-erbα, and that antagonizing the activity of rev-erbα ablated the enhanced inflammatory response induced by LPS in the heme primed cells. Conclusion: These data provide evidence that hemolysis may play an important role in the hyper-inflammatory monocyte response via heme- induced dysregulation of the circadian clock. These novel observations provide entirely new avenues of anti-inflammatory therapy in SCD. Disclosures No relevant conflicts of interest to declare.

P201 FATTY ACIDS INDUCE A PRO-INFLAMMATORY GENE EXPRESSION PROFILE IN HUH-7 CELLS AND ATTENUATE THE ANTI-HCV ACTION OF INTERFERON

2014 ◽  
Vol 60 (1) ◽  
pp. S133
Author(s):  
E.Y. Tse ◽  
K.J. Helbig ◽  
K. Van der Hoek ◽  
E.M. McCartney ◽  
J. George ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fatty Acids ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Inflammatory Gene Expression ◽  
Inflammatory Gene

scholarly journals Non-invasively triggered spreading depolarizations induce a rapid pro-inflammatory response in cerebral cortex

2019 ◽  
Vol 40 (5) ◽  
pp. 1117-1131 ◽  
Author(s):  
Tsubasa Takizawa ◽  
Tao Qin ◽  
Andreia Lopes de Morais ◽  
Kazutaka Sugimoto ◽  
Joon Yong Chung ◽  
...  
Keyword(s):  
Gene Expression ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Inflammatory Gene Expression ◽  
Inflammatory Gene ◽  
Tnf Α ◽  
Inflammatory Processes ◽  
Factor Α ◽  
The Relationship

Cortical spreading depolarization (CSD) induces pro-inflammatory gene expression in brain tissue. However, previous studies assessing the relationship between CSD and inflammation have used invasive methods that directly trigger inflammation. To eliminate the injury confounder, we induced CSDs non-invasively through intact skull using optogenetics in Thy1-channelrhodopsin-2 transgenic mice. We corroborated our findings by minimally invasive KCl-induced CSDs through thinned skull. Six CSDs induced over 1 h dramatically increased cortical interleukin-1β (IL-1β), chemokine (C-C motif) ligand 2 (CCL2), and tumor necrosis factor-α (TNF-α) mRNA expression peaking around 1, 2 and 4 h, respectively. Interleukin-6 (IL-6) and intercellular adhesion molecule-1 (ICAM-1) were only modestly elevated. A single CSD also increased IL-1β, CCL2, and TNF-α, and revealed an ultra-early IL-1β response within 10 min. The response was blunted in IL-1 receptor-1 knockout mice, implicating IL-1β as an upstream mediator, and suppressed by dexamethasone, but not ibuprofen. CSD did not alter systemic inflammatory indices. In summary, this is the first report of pro-inflammatory gene expression after non-invasively induced CSDs. Altogether, our data provide novel insights into the role of CSD-induced neuroinflammation in migraine headache pathogenesis and have implications for the inflammatory processes in acute brain injury where numerous CSDs occur for days.

scholarly journals Effect of Dietary Fatty Acids on Inflammatory Gene Expression in Healthy Humans

2009 ◽  
Vol 284 (23) ◽  
pp. 15400-15407 ◽  
Author(s):  
Kelly L. Weaver ◽  
Priscilla Ivester ◽  
Michael Seeds ◽  
L. Douglas Case ◽  
Jonathan P. Arm ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fatty Acids ◽  
Dietary Fatty Acids ◽  
Inflammatory Gene Expression ◽  
Inflammatory Gene ◽  
Healthy Humans
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