scholarly journals D-mannose suppresses macrophage IL-1β production

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Simone Torretta ◽  
Alessandra Scagliola ◽  
Luisa Ricci ◽  
Francesco Mainini ◽  
Sabrina Di Marco ◽  
...  
Keyword(s):  
Mouse Model ◽  
Macrophage Activation ◽  
T Cell Differentiation ◽  
Activated Macrophages ◽  
Phosphomannose Isomerase ◽  
Inflammatory Conditions ◽  
Consequent Reduction ◽  
Inflammatory Macrophages ◽  
Mannose Metabolism

AbstractD-mannose is a monosaccharide approximately a hundred times less abundant than glucose in human blood. Previous studies demonstrated that supraphysiological levels of D-mannose inhibit tumour growth and stimulate regulatory T cell differentiation. It is not known whether D-mannose metabolism affects the function of non-proliferative cells, such as inflammatory macrophages. Here, we show that D-mannose suppresses LPS-induced macrophage activation by impairing IL-1β production. In vivo, mannose administration improves survival in a mouse model of LPS-induced endotoxemia as well as decreases progression in a mouse model of DSS-induced colitis. Phosphomannose isomerase controls response of LPS-activated macrophages to D-mannose, which impairs glucose metabolism by raising intracellular mannose-6-phosphate levels. Such alterations result in the suppression of succinate-mediated HIF-1α activation, imposing a consequent reduction of LPS-induced Il1b expression. Disclosing an unrecognized metabolic hijack of macrophage activation, our study points towards safe D-mannose utilization as an effective intervention against inflammatory conditions.

scholarly journals Effects of Thymus vulgaris L., Cinnamomum verum J.Presl and Cymbopogon nardus (L.) Rendle Essential Oils in the Endotoxin-induced Acute Airway Inflammation Mouse Model

Molecules ◽  
2020 ◽  
Vol 25 (15) ◽  
pp. 3553
Author(s):  
Eszter Csikós ◽  
Kata Csekő ◽  
Amir Reza Ashraf ◽  
Ágnes Kemény ◽  
László Kereskai ◽  
...  
Keyword(s):  
Mouse Model ◽  
Essential Oils ◽  
Airway Inflammation ◽  
Airway Hyperresponsiveness ◽  
Whole Body ◽  
Gas Chromatography Mass Spectrometry ◽  
Thymus Vulgaris ◽  
Inflammatory Conditions ◽  
Inflammatory Parameters

Thyme (TO), cinnamon (CO), and Ceylon type lemongrass (LO) essential oils (EOs) are commonly used for inhalation. However, their effects and mechanisms on inflammatory processes are not well-documented, and the number of in vivo data that would be important to determine their potential benefits or risks is low. Therefore, we analyzed the chemical composition and investigated the activity of TO, CO, and LO on airway functions and inflammatory parameters in an acute pneumonitis mouse model. The components of commercially available EOs were measured by gas chromatography–mass spectrometry. Airway inflammation was induced by intratracheal endotoxin administration in mice. EOs were inhaled during the experiments. Airway function and hyperresponsiveness were determined by unrestrained whole-body plethysmography on conscious animals. Myeloperoxidase (MPO) activity was measured by spectrophotometry from lung tissue homogenates, from which semiquantitative histopathological scores were assessed. The main components of TO, CO, and LO were thymol, cinnamaldehyde, and citronellal, respectively. We provide here the first evidence that TO and CO reduce inflammatory airway hyperresponsiveness and certain cellular inflammatory parameters, so they can potentially be considered as adjuvant treatments in respiratory inflammatory conditions. In contrast, Ceylon type LO inhalation might have an irritant effect (e.g., increased airway hyperresponsiveness and MPO activity) on the inflamed airways, and therefore should be avoided.

scholarly journals Spirulina supplementation in a mouse model of diet-induced liver fibrosis reduced the pro-inflammatory response of splenocytes

2019 ◽  
Vol 121 (7) ◽  
pp. 748-755 ◽  
Author(s):  
Tho X. Pham ◽  
Yoojin Lee ◽  
Minkyung Bae ◽  
Siqi Hu ◽  
Hyunju Kang ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Mouse Model ◽  
High Cholesterol Diet ◽  
Appreciable Effect ◽  
Healthy Foods ◽  
Inflammatory Gene Expression ◽  
Inflammatory Conditions ◽  
Alanine Aminotransferase Level ◽  
High Sucrose

AbstractTreatment of liver fibrosis is very limited as there is currently no effective anti-fibrotic therapy. Spirulina platensis (SP) is a blue-green alga that is widely supplemented in healthy foods. The objective of this study was to determine whether SP supplementation can prevent obesity-induced liver fibrosis in vivo. Male C57BL/6J mice were randomly assigned to a low-fat or a high-fat (HF)/high-sucrose/high-cholesterol diet or an HF diet supplemented with 2·5 % SP (w/w) (HF/SP) for 16 or 20 weeks. There were no significant differences in body weight, activity, energy expenditure, serum lipids or glucose tolerance between mice on HF and HF/SP diets. However, plasma alanine aminotransferase level was significantly reduced by SP at 16 weeks. Expression of fibrotic markers and trichrome stains showed no differences between HF and HF/SP. Splenocytes isolated from HF/SP fed mice had lower inflammatory gene expression and cytokine secretion compared with splenocytes from HF-fed mice. SP supplementation did not attenuate HF-induced liver fibrosis. However, the expression and secretion of inflammatory genes in splenocytes were significantly reduced by SP supplementation, demonstrating the anti-inflammatory effects of SP in vivo. Although SP did not show appreciable effect on the prevention of liver fibrosis in this mouse model, it may be beneficial for other inflammatory conditions.

In vivo monitoring of activated macrophages and neutrophils in response to ischemic osteonecrosis in a mouse model

2015 ◽  
Vol 34 (2) ◽  
pp. 307-313 ◽  
Author(s):  
Matthew C. Phipps ◽  
YiHui Huang ◽  
Ryosuke Yamaguchi ◽  
Nobuhiro Kamiya ◽  
Naga S. Adapala ◽  
...  
Keyword(s):  
Mouse Model ◽  
Activated Macrophages ◽  
In Vivo Monitoring ◽  
Ischemic Osteonecrosis

scholarly journals CELL-MEDIATED IMMUNITY AGAINST BESNOITIA AND TOXOPLASMA IN SPECIFICALLY AND CROSS-IMMUNIZED HAMSTERS AND IN CULTURES

1974 ◽  
Vol 139 (3) ◽  
pp. 560-580 ◽  
Author(s):  
Richard L. Hoff ◽  
J. K. Frenkel
Keyword(s):  
Macrophage Activation ◽  
Cell Formation ◽  
Lymphoid Cells ◽  
Cell Populations ◽  
Cell Mediated Immunity ◽  
Activated Macrophages ◽  
Specific Effects ◽  
Giant Cell Formation

The capacity of hamster peritoneal cell populations to control viability and growth of Besnoitia and Toxoplasma organisms was assessed in vivo and in vitro. Immunized hamsters reduced the homologous organisms 100- to 10,000-fold over a 5-day period, but the heterologous infection increased 100- to 1,000-fold in numbers, similar as in the nonimmune controls. Passively administered antibody was ineffective although lytic cofactors were supplied by hamsters. In cultures, peritoneal cells from Besnoitia-immune hamsters delayed the growth of homologous parasites to an average of 38.5 h per division; however, in Toxoplasma-immune and nonimmune cells, Besnoitia divided every 12.8 h. Specificity of immunity was pronounced against both infections. With cross-infections, Toxoplasma-immune cultures did not effectively delay Besnoitia growth; however, Besnoitia-immune cultures reduced Toxoplasma growth by one-half. Co-cultivation experiments demonstrated that specifically committed lymphocytes could instruct macrophages to reduce the homologous organism 10-fold, whereas heterologous organisms were reduced only 2-fold. Lymphocyte supernatants initiated hypersensitivity as indicated by macrophage activation and giant cell formation in culture. However, these supernatants did not transfer infection immunity. Lymphokines could account for the hypersensitivity phenomena, but cell-mediated infection immunity in this model required close lymphocyte-macrophage proximity. These studies indicate that a number of distinct processes including delayed hypersensitivity, macrophage activation, and specific cellular immunity are acting simultaneously during latent Besnoitia infection of hamsters. All three processes are mediated by lymphoid cells and appear to be specifically induced. Although activated macrophages develop some heightened nonspecific capabilities, these were several orders of magnitude below the specific effects.

scholarly journals Regulation of arachidonic acid metabolism by macrophage activation.

1982 ◽  
Vol 155 (4) ◽  
pp. 1148-1160 ◽  
Author(s):  
W A Scott ◽  
N A Pawlowski ◽  
H W Murray ◽  
M Andreach ◽  
J Zrike ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Macrophage Activation ◽  
Peritoneal Macrophages ◽  
Arachidonic Acid Metabolism ◽  
Prostaglandin Synthesis ◽  
Activated Macrophages ◽  
Synthetic Enzymes ◽  
Oxygenated Products

Levels of zymosan-induced arachidonic acid (20:4) metabolism by peritoneal macrophages elicited with inflammatory agents and resident macrophages were similar. Thyioglycollate (THIO)-elicited macrophages represented the exception; however, the diminished metabolism by these cells was reproduced by exposing resident cells to 5 mg/ml THIO broth in vitro. In contrast, reduced prostaglandin synthesis by macrophages from mice variously treated with the immunologic agents, Corynebacterium parvum or Bacille Calmette Guérin (BCG), closely correlated with enhanced antitoxoplasma activity, one measure of macrophage activation. This relationship, although not causative, suggested that the capacity for 20:4 metabolism is a function of the macrophage activation state. Modulation of macrophage 20:4 metabolism in vivo apparently required factors in addition to lymphocyte-derived products. Treatment of resident macrophages in vitro with BCG lymphokine was without effect on 20:4 release or prostaglandin synthesis. Activated macrophages from animals inoculated i.p. with C. parvum exhibited reduced 20:4 release and also failed to metabolize 70% of the 20:4 released in response to a zymosan stimulus. Consequently, the quantities of 20:4 metabolites formed were significantly less than expected from 20:4 release. These activated macrophages displayed greatly reduced synthesis of prostacylcin and leukotriene C compared with other 20:4 metabolites. It appeared that factors that regulate macrophage 20:4 metabolism influence the level of the inducible phospholipase and synthetic enzymes for specific 20:4 oxygenated products.

scholarly journals A transgenic mouse model to analyze CD8+ effector T cell differentiation in vivo

1999 ◽  
Vol 96 (24) ◽  
pp. 13932-13937 ◽  
Author(s):  
N. Manjunath ◽  
P. Shankar ◽  
B. Stockton ◽  
P. D. Dubey ◽  
J. Lieberman ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
T Cell ◽  
Mouse Model ◽  
Transgenic Mouse ◽  
Transgenic Mouse Model ◽  
T Cell Differentiation ◽  
Effector T Cell

scholarly journals Osthole Attenuates Macrophage Activation in Experimental Asthma by Inhibitingthe NF-ĸB/MIF Signaling Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Ruyi Li ◽  
Peng Song ◽  
Guofang Tang ◽  
Jianghong Wei ◽  
Lizong Rao ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Macrophage Activation ◽  
Inflammatory Cells ◽  
Activated Macrophages ◽  
Arginase 1 ◽  
Coumarin Compound ◽  
And Migration ◽  
Cluster Of Differentiation

Inhibition of activated macrophages is an alternative therapeutic strategy for asthma. We investigated whether a coumarin compound, osthole, isolated from Cnidiummonnieri (L.) Cuss, alleviated macrophage activation in vivo and in vitro. Osthole could reduce expression of a marker of activated macrophages, cluster of differentiation (CD)206, in an ovalbumin-challenge model of asthma in mice. Osthole could also inhibit infiltration of inflammatory cells, collagen deposition and production of proinflammatory cytokines [interleukin (IL)-1β, tumor necrosis factor-ɑ, macrophage migration inhibitory factor (MIF)] in asthmatic mice. In vitro, expression of phosphorylated-IĸBɑ, MIF and M2 cytokines (Ym-1, Fizz-1, arginase-1) in IL-4-induced macrophages decreased upon exposure to the NF-ĸB inhibitor MG-132. In our short hairpin (sh)RNA-MIF-knockdown model, reduced expression of M2 cytokines was detected in the IL-4 + shRNA-MIF group. Osthole could attenuate the proliferation and migration of an IL-4-induced rat alveolar macrophages line (NR8383). Osthole could reduce IL-4-induced translocation of nuclear factor-kappa B (NF-ĸB) in NR8383 cells. Collectively, our results suggest that osthole ameliorates macrophage activation in asthma by suppressing the NF-ĸB/MIF signaling pathway, and might be a potential agent for treating asthma.

scholarly journals Collagen-derived peptide, DGEA, inhibits pro-inflammatory macrophages in biofunctional hydrogels

2021 ◽  
Author(s):  
Aakanksha Jha ◽  
Erika Moore
Keyword(s):  
Macrophage Activation ◽  
Innate Immune ◽  
M1 Macrophages ◽  
Inflammatory Conditions ◽  
M1 Macrophage ◽  
Inflammatory Stimuli ◽  
Poly Ethylene ◽  
Inflammatory Macrophages ◽  
Inflammatory Macrophage

AbstractMacrophages are innate immune cells that play important roles in wound healing. Particularly, M1 macrophages are considered pro‐inflammatory and promote initial phases of inflammation. Long-term exposure to inflammatory stimuli causes an increase in M1 macrophages, which contributes to chronic inflammation. Activated M1 macrophages have been shown to upregulate integrin α2β1 expression. To interfere with α2β1 binding, we designed a biofunctional hydrogel utilizing a collagen I-derived peptide, DGEA (Asp-Gly-Glu-Ala). We hypothesize that M1 macrophage activation can be reduced in the presence of DGEA. Effects of DGEA on M1 macrophages were studied via soluble delivery and immobilization within poly(ethylene glycol) (PEG) hydrogels. We demonstrate that M1 macrophage activation is reduced both via soluble delivery of DGEA in 2D and via immobilized DGEA in a 3D PEG-DGEA hydrogel. This novel biomaterial can manipulate inflammatory macrophage activation and can be applied to prevent chronic inflammatory conditions via macrophage manipulation. Graphical abstract

Abstract 649: PARP14 and PARP9 Are Novel Regulators of Macrophage Activation

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Hiroshi Iwata ◽  
Piero Ricchiuto ◽  
Takuya Hara ◽  
Amitabh Sharma ◽  
Alex Mojcher ◽  
...  
Keyword(s):  
Macrophage Activation ◽  
Macrophage Polarization ◽  
Vascular Diseases ◽  
Interleukin 4 ◽  
Human Macrophage ◽  
Physical Interaction ◽  
Anti Inflammatory ◽  
Inflammatory Macrophages

Purpose: A microenvironment dominant in pro-inflammatory macrophages (“M1”) and lacking anti-inflammatory macrophages (“M2”) may promote vascular diseases. We explored and validated key regulators of such macrophage polarization. Methods and Results: Using global proteomic analysis and bioinformatics, we examined the changes in the proteomes of mouse and human macrophage cell lines (RAW264.7; THP-1) in response to interferon gamma (IFNγ) or interleukin 4 (IL-4) for M1 or M2 polarization, respectively. Among 5816 proteins in RAW264.7 and 4723 in THP-1, data filtering and clustering identified poly(ADP-ribose) polymerase 14 (PARP14) and 9 (PARP9) as candidates for key regulators of macrophage polarization, which increase in M1 and decrease in M2 condition. siRNA silencing of PARP14 in macrophages induced M1 genes TNF-α, IL-1β and iNOS, while decreased M2 markers Arg1 and MRC1, indicating that PARP14 suppresses pro-inflammatory macrophage activation and promotes anti-inflammatory polarization. PARP14 silencing induced STAT1 phosphorylation and reduced STAT6 phosphorylation, suggesting their roles in the underlying signaling mechanisms. In contrast, PARP9 silencing decreased M1 markers, as well as phosphorylation of STAT1. Of interest, a direct physical interaction between PARP14 and PARP9 was also demonstrated. In vivo evidence supported these in vitro findings. Macrophages of PARP14-deficient mice expressed markedly higher levels of M1 genes and lower levels M2 markers. PARP14 deficiency accelerated lesion development after mechanical injury in femoral arteries. Conclusions: PARP14 and PARP9 regulate macrophage activation, offering novel therapeutic targets for vascular diseases.

scholarly journals Lactate and IL6 define separable paths of inflammatory metabolic adaptation

2021 ◽  
Vol 7 (26) ◽  
pp. eabg3505
Author(s):  
Stefanie Dichtl ◽  
Laura Lindenthal ◽  
Leonie Zeitler ◽  
Kristina Behnke ◽  
Daniela Schlösser ◽  
...  
Keyword(s):  
Gene Expression ◽  
Tissue Repair ◽  
Macrophage Activation ◽  
Metabolic Adaptation ◽  
M2 Macrophage ◽  
Activated Macrophages ◽  
Inflammatory Stress ◽  
Arginase 1 ◽  
Expression Of Genes ◽  
Inflammatory Macrophages

Lactate is an end point of Warburg-type metabolism found in inflammatory macrophages. Recently, lactate was shown to modify histones of lipopolysaccharide (LPS)–activated macrophages in a time-dependent way and promote the expression of genes linked to tissue repair, including arginase-1 (Arg1). We tested the interrelationships between histone lactylation (Kla) and tissue reparative gene expression and found that Kla was uncoupled from changes in gene expression linked to resolving M2 macrophage activation but correlated with Arg1 expression. LPS-induced Arg1 was instead dependent on autocrine-paracrine interleukin-6 (IL6) production, the IL6 receptor, and Stat3 signal transduction. We found that Kla increases as macrophages prepare to die under inflammatory stress, and Kla was absent in macrophages that cannot generate reactive nitrogen or have defects in diverse macrophage death pathways. Thus, Kla is a consequence rather than a cause of macrophage activation but occurs coincidently with an IL6- and Arg1-dependent metabolic rewiring under inflammatory duress.

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