scholarly journals Oxylipin Profiles as Functional Characteristics of Acute Inflammatory Responses in Astrocytes Pre-Treated with IL-4, IL-10, or LPS

2020 ◽  
Vol 21 (5) ◽  
pp. 1780 ◽  
Author(s):  
Dmitry V. Chistyakov ◽  
Gleb E. Gavrish ◽  
Sergei V. Goriainov ◽  
Viktor V. Chistyakov ◽  
Alina A. Astakhova ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Polyunsaturated Fatty Acid ◽  
Inflammatory Responses ◽  
Interleukin 4 ◽  
Cell Reactivity ◽  
Gene Markers ◽  
Inflammatory Stimuli ◽  
Inflammatory Phenotype ◽  
Anti Inflammatory ◽  
Rat Astrocyte

Functional phenotypes, which cells can acquire depending on the microenvironment, are currently the focus of investigations into new anti-inflammatory therapeutic approaches. Glial cells, microglia, and astrocytes are major participants in neuroinflammation, but their roles differ, as microglia are cells of mesodermal origin, while astrocytes are cells of ectodermal origin. The inflammatory phenotype of cells can be modulated by ω-6- and ω-3-polyunsaturated fatty acid-derived oxylipins, although data on changes in oxylipin profiles in different cell adaptations to pro- and anti-inflammatory stimuli are scarce. Our study aimed to compare UPLC-MS/MS-measured oxylipin profiles in various rat astrocyte adaptation states. We used cells treated for 24 h with lipopolysaccharide (LPS) for classical pro-inflammatory adaptation and with interleukin 4 (IL-4) or 10 (IL-10) for alternative anti-inflammatory adaptation, with the resulting phenotypes characterized by quantitative real-time PCR (RT-PCR). We also tested long-term, low-concentration LPS treatment (endotoxin treatment) as a model of astrocyte adaptations. The functional response of astrocytes was estimated by acute (4 h) LPS-induced cell reactivity, measured by gene expression markers and oxylipin synthesis. We discovered that, as well as gene markers, oxylipin profiles can serve as markers of pro- (A1-like) or anti-inflammatory (A2-like) adaptations. We observed predominant involvement of ω-6 polyunsaturated fatty acid (PUFA) and the cyclooxygenase branch for classical (LPS) pro-inflammatory adaptations and ω-3 PUFA and the lipoxygenase branch for alternative (IL-4) anti-inflammatory adaptations. Treatment with IL-4, but not IL-10, primes the ability of astrocytes to activate the innate immunity signaling pathways in response to LPS. Endotoxin-treated astrocytes provide an alternative anti-inflammatory adaptation, which makes cells less sensitive to acute LPS stimulation than the IL-4 induced adaptation. Taken together, the data reveal that oxylipin profiles associate with different states of polarization to generate a pro-inflammatory or anti-inflammatory phenotype. This association manifests itself both in native cells and in their responses to a pro-inflammatory stimulus.

scholarly journals Activation and Regulation of Cellular Eicosanoid Biosynthesis

2007 ◽  
Vol 7 ◽  
pp. 1273-1284 ◽  
Author(s):  
Thomas G. Brock ◽  
Marc Peters-Golden
Keyword(s):  
Arachidonic Acid ◽  
Fatty Acid ◽  
Polyunsaturated Fatty Acid ◽  
Inflammatory Responses ◽  
Physiological Responses ◽  
Cell Types ◽  
Key Points ◽  
Enzymatic Pathways

There is a growing appreciation for the wide variety of physiological responses that are regulated by lipid messengers. One particular group of lipid messengers, the eicosanoids, plays a central role in regulating immune and inflammatory responses in a receptor-mediated fashion. These mediators are related in that they are all derived from one polyunsaturated fatty acid, arachidonic acid. However, the various eicosanoids are synthesized by a wide variety of cell types by distinct enzymatic pathways, and have diverse roles in immunity and inflammation. In this review, the major pathways involved in the synthesis of eicosanoids, as well as key points of regulation, are presented.

scholarly journals Inhibitor of Hyaluronic Acid Synthesis 4-Methylumbelliferone as an Anti-Inflammatory Modulator of LPS-Mediated Astrocyte Responses

2020 ◽  
Vol 21 (21) ◽  
pp. 8203 ◽  
Author(s):  
Dmitry V. Chistyakov ◽  
Arina I. Nikolskaya ◽  
Sergei V. Goriainov ◽  
Alina A. Astakhova ◽  
Marina G. Sergeeva
Keyword(s):  
Hyaluronic Acid ◽  
Inflammatory Responses ◽  
Specific Inhibitor ◽  
Acid Synthesis ◽  
Interleukin 10 ◽  
Ultra Performance Liquid Chromatography ◽  
Necrosis Factor Alpha ◽  
Inflammatory Stimuli ◽  
Anti Inflammatory ◽  
Ha Synthase

Astrocytes are glial cells that play an important role in neuroinflammation. Astrocytes respond to many pro-inflammatory stimuli, including lipopolysaccharide (LPS), an agonist of Toll-like receptor 4 (TLR4). Regulatory specificities of inflammatory signaling pathways are still largely unknown due to the ectodermal origin of astrocytes. Recently, we have shown that hyaluronic acid (HA) may form part of astrocyte inflammatory responses. Therefore, we tested 4-methylumbelliferone (4-MU), a specific inhibitor of HA synthesis, as a possible regulator of LPS-mediated responses. Rat primary astrocytes were treated with LPS with and without 4-MU and gene expression levels of inflammatory (interleukins 1β, (IL-1β), 6, (IL-6), tumor necrosis factor alpha TNFα,) and resolution interleukin 10 (IL-10) markers were evaluated via real-time PCR and western blot. The release of cytokines and HA was determined by ELISA. Oxylipin profiles were measured by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis. Our data show that 4-MU (i) has anti-inflammatory effects in the course of TLR4 activation, decreasing the cytokines level TNFα, IL-6 and IL-1β and increasing IL-10, (ii) downregulates prostaglandin synthesis but not via cyclooxygenases COX-1 and COX-2 pathways, (iii) modulates HA synthesis and decreases LPS-induced HA synthase mRNA expression (HAS-1, HAS-2) but does not have an influence on HAS-3, HYAL1 and HYAL2 mRNAs; (iv) the effects of 4-MU are predominantly revealed via JNK but not p38, ERK mitogen-activated protein kinases (MAPKs) or nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) pathways. For the first time, it is shown that 4-MU possesses the useful potential to regulate an inflammatory astrocyte response.

scholarly journals Diet Supplementation in ω3 Polyunsaturated Fatty Acid Favors an Anti-Inflammatory Basal Environment in Mouse Adipose Tissue

Nutrients ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 438 ◽  
Author(s):  
Cecilia Colson ◽  
Rayane Ghandour ◽  
Océane Dufies ◽  
Samah Rekima ◽  
Agnès Loubat ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Inflammatory Response ◽  
Polyunsaturated Fatty Acids ◽  
Polyunsaturated Fatty Acid ◽  
Inflammatory Cytokine ◽  
M2 Macrophage ◽  
Anti Inflammatory ◽  
Diet Supplementation

Oxylipins are metabolized from dietary ω3 and ω6 polyunsaturated fatty acids and are involved in an inflammatory response. Adipose tissue inflammatory background is a key factor of metabolic disorders and it is accepted that dietary fatty acids, in terms of quality and quantity, modulate oxylipin synthesis in this tissue. Moreover, it has been reported that diet supplementation in ω3 polyunsaturated fatty acids resolves some inflammatory situations. Thus, it is crucial to assess the influence of dietary polyunsaturated fatty acids on oxylipin synthesis and their impact on adipose tissue inflammation. To this end, mice fed an ω6- or ω3-enriched standard diet (ω6/ω3 ratio of 30 and 3.75, respectively) were analyzed for inflammatory phenotype and adipose tissue oxylipin content. Diet enrichment with an ω3 polyunsaturated fatty acid induced an increase in the oxylipins derived from ω6 linoleic acid, ω3 eicosapentaenoic, and ω3 docosahexaenoic acids in brown and white adipose tissues. Among these, the level of pro-resolving mediator intermediates, as well as anti-inflammatory metabolites, were augmented. Concomitantly, expressions of M2 macrophage markers were increased without affecting inflammatory cytokine contents. In vitro, these metabolites did not activate macrophages but participated in macrophage polarization by inflammatory stimuli. In conclusion, we demonstrated that an ω3-enriched diet, in non-obesogenic non-inflammatory conditions, induced synthesis of oxylipins which were involved in an anti-inflammatory response as well as enhancement of the M2 macrophage molecular signature, without affecting inflammatory cytokine secretion.

scholarly journals Anti-inflammatory effect of Varthemia iphionoides extracts against prostate cancer in vitro

2017 ◽  
Vol 15 (1) ◽  
pp. 8-14 ◽  
Author(s):  
Ala’a Al-Bakheit ◽  
Saeid Abu-Romman ◽  
Ahmad Sharab ◽  
Mohammad Al Shhab
Keyword(s):  
Medicinal Plant ◽  
Interleukin 6 ◽  
Inflammatory Responses ◽  
Anticancer Activities ◽  
Methanolic Extracts ◽  
Inflammatory Stimuli ◽  
Pc3 Cells ◽  
Anti Inflammatory ◽  
Inflammatory Effect

Varthemia iphionoides is a Jordanian medicinal plant with several health-promoting properties, including antibacterial, antioxidant and anticancer activities. However, its anti-inflammatory properties have been poorly investigated up to date. The current study aimed to investigate the anti-inflammatory effect of V. iphionoides by measuring the production of interleukin-6 in response to a pro-inflammatory stimulus (bacterial lipopolysaccharide) in in vitro cell models of human MRC-5 and PC3 cells. We observed a significant reduction in lipopolysaccharide-induced interleukin-6 release in response to V. iphionoides (125 µg/mL) in both non-cancerous fibroblast MRC-5 and prostate cancerous PC3 cells. However, the anti-inflammatory effect of this medicinal plant was stronger when MRC-5 cells were treated with an aqueous extract, while the methanolic extract was more potent in PC3 cells. The effect of V. iphionoides in reducing interleukin-6 production was not due to its cytotoxicity, and future studies are required to elucidate the mechanisms of action by which this medicinal plant modulates inflammatory responses. In conclusion, the results of our study represent the first report of the potential protective effect of water and methanolic extracts of V. iphionoides against pro-inflammatory stimuli in fibroblasts and cancer cells of human origin, and it is critically important to identify the phytochemical compounds responsible for this effect.

scholarly journals Differential Use of Chondroitin Sulfate to Regulate Hyaluronan Binding by Receptor CD44 in Inflammatory and Interleukin 4-activated Macrophages

2011 ◽  
Vol 286 (22) ◽  
pp. 19179-19190 ◽  
Author(s):  
Brian Ruffell ◽  
Grace F. T. Poon ◽  
Sally S. M. Lee ◽  
Kelly L. Brown ◽  
Sie-Lung Tjew ◽  
...  
Keyword(s):  
Chondroitin Sulfate ◽  
Cell Surface Receptor ◽  
Interleukin 4 ◽  
Mouse Bone Marrow ◽  
Activated Macrophages ◽  
Cd44 Expression ◽  
Mouse Macrophages ◽  
Inflammatory Stimuli ◽  
Anti Inflammatory ◽  
Hyaluronan Binding

CD44 is a cell surface receptor for the extracellular matrix glycosaminoglycan hyaluronan and is involved in processes ranging from leukocyte recruitment to wound healing. In the immune system, the binding of hyaluronan to CD44 is tightly regulated, and exposure of human peripheral blood monocytes to inflammatory stimuli increases CD44 expression and induces hyaluronan binding. Here we sought to understand how mouse macrophages regulate hyaluronan binding upon inflammatory and anti-inflammatory stimuli. Mouse bone marrow-derived macrophages stimulated with tumor necrosis factor α or lipopolysaccharide and interferon-γ (LPS/IFNγ) induced hyaluronan binding by up-regulating CD44 and down-regulating chondroitin sulfation on CD44. Hyaluronan binding was induced to a lesser extent in interleukin-4 (IL-4)-activated macrophages despite increased CD44 expression, and this was attributable to increased chondroitin sulfation on CD44, as treatment with β-d-xyloside to prevent chondroitin sulfate addition significantly enhanced hyaluronan binding. These changes in the chondroitin sulfation of CD44 were associated with changes in mRNA expression of two chondroitin sulfotransferases, CHST3 and CHST7, which were decreased in LPS/IFNγ-stimulated macrophages and increased in IL-4-stimulated macrophages. Thus, inflammatory and anti-inflammatory stimuli differentially regulate the chondroitin sulfation of CD44, which is a dynamic physiological regulator of hyaluronan binding by CD44 in mouse macrophages.

scholarly journals Trem2promotes anti-inflammatory responses in microglia and is suppressed under pro-inflammatory conditions

2018 ◽  
Author(s):  
Wenfei Liu ◽  
Orjona Taso ◽  
Rui Wang ◽  
Sevinc Bayram ◽  
Pablo Garcia-Reitboeck ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Inflammatory Responses ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Similar Expression Profile ◽  
Inflammatory Conditions ◽  
Phenotype Comparison ◽  
Inflammatory Phenotype ◽  
Similar Phenotype ◽  
Anti Inflammatory

AbstractGenome-wide association studies have reported that, amongst other microglial genes, variants inTREM2can profoundly increase the incidence of developing Alzheimer’s disease (AD). We have investigated the role of TREM2 in primary microglial cultures from wild type mice by using siRNA to decreaseTrem2expression, and in parallel from knock-in mice heterozygous or homozygous for theTrem2R47H AD risk variant. The prevailing phenotype ofTrem2R47H knock-in mice was decreased expression levels ofTrem2in microglia, which resulted in decreased density of microglia in the hippocampus. Overall, primary microglia with reducedTrem2expression, either by siRNA or from the R47H knock-in mice, displayed a similar phenotype. Comparison of the effects of decreasedTrem2expression under conditions of LPS pro-inflammatory or IL-4 anti-inflammatory stimulation revealed the importance ofTrem2in driving a number of the genes up-regulated in the anti-inflammatory phenotype. RNA-seq analysis showed that IL-4 induced the expression of a programme of genes includingArg1andAp1b1in microglia, which showed an attenuated response to IL-4 whenTrem2expression was decreased. Genes showing a similar expression profile toArg1were enriched for STAT6 transcription factor recognition elements in their promoter, andTrem2knockdown decreased levels of the transcription factor STAT6. LPS-induced pro-inflammatory stimulation suppressedTrem2expression, thus preventing TREM2’s anti-inflammatory drive. Given that anti-inflammatory signaling is associated with tissue repair, understanding the signaling mechanisms downstream ofTrem2in coordinating the pro- and anti-inflammatory balance of microglia, particularly mediating effects of the IL-4-regulated anti-inflammatory pathway, has important implications for fighting neurodegenerative disease.Graphical abstract

scholarly journals Anti-Inflammatory and Proresolving Effects of the Omega-6 Polyunsaturated Fatty Acid Adrenic Acid

2020 ◽  
Vol 205 (10) ◽  
pp. 2840-2849
Author(s):  
Hilde Brouwers ◽  
Hulda S. Jónasdóttir ◽  
Marije E. Kuipers ◽  
Joanneke C. Kwekkeboom ◽  
Jennifer L. Auger ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Polyunsaturated Fatty Acid ◽  
Omega 6 ◽  
Adrenic Acid ◽  
Anti Inflammatory

scholarly journals Bioenergetic programming of macrophages by the apolipoprotein A-I mimetic peptide 4F

2015 ◽  
Vol 467 (3) ◽  
pp. 517-527 ◽  
Author(s):  
Geeta Datta ◽  
Philip A. Kramer ◽  
Michelle S. Johnson ◽  
Hirotaka Sawada ◽  
Lesley E. Smythies ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Oxidative Metabolism ◽  
Fatty Acid Uptake ◽  
Acid Uptake ◽  
Mimetic Peptide ◽  
Apolipoprotein A ◽  
Inflammatory Phenotype ◽  
Anti Inflammatory ◽  
Mitochondrial Oxidative Metabolism

4F-mediated differentiation of monocyte-derived macrophages to an anti-inflammatory phenotype is due, in part, to an increase in fatty acid uptake and mitochondrial oxidative metabolism.

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