Postprandial triglyceride-rich lipoproteins promote lipid accumulation and apolipoprotein B-48 receptor transcriptional activity in human circulating and murine bone marrow neutrophils in a fatty acid-dependent manner

Sorafenib has been used for the treatment of liver cancer. However, its clinical impact on human immunity system remains poorly known. Our previous study has shown that sorafenib modulates immunosuppressive cell populations in murine liver cancer models. Here, we continue to report that low doses of sorafenib promotes the survival of murine bone marrow cells (BMCs) in a dose-dependent manner by up-regulating the anti-apoptotic protein survivin. Sorafenib induces differentiation of BMCs into suppressive dendritic cells that inhibit autologous T-cell proliferation and stimulate CD4+ T cells to express increased IL-1β, IL-2, IL-4, IL-10, IFN-γ and TNF-α, and reduced levels of IL-6 and CD25, which indicates that sorafenib-induced dendritic cells represent a distinct cellular subset with unique properties. Taken together, our findings suggest that in addition to its anticancer effects, sorafenib has an immunoregulatory property that is apparent at low doses.

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Enterococcus faecalis Induces Differentiation of Immune-Aberrant Dendritic Cells from Murine Bone Marrow-Derived Stem Cells

Infection and Immunity ◽

10.1128/iai.00338-20 ◽

2020 ◽

Vol 88 (11) ◽

Author(s):

Mohamed Mohamed Elashiry ◽

Mahmoud Elashiry ◽

Rana Zeitoun ◽

Ranya Elsayed ◽

Fucong Tian ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Dendritic Cells ◽

Enterococcus Faecalis ◽

Transforming Growth Factor ◽

Interleukin 4 ◽

Dependent Manner ◽

Immune Functions ◽

Content Type ◽

Murine Bone Marrow

ABSTRACT Enterococcus faecalis, long implicated in serious systemic infections and failure of root canal treatment, is a persistent inhabitant of oral periapical lesions. Dendritic cells (DCs) and other innate immune cells patrol the oral mucosa for infecting microbes. Dendritic cells are efficient at capturing microbes when immature, whereupon they can transform into potent antigen-presenting cells upon full maturation. Autophagy, a sophisticated intracellular process first described for elimination of damaged organelles, regulates DC maturation and other important immune functions of DCs. The present study examined how E. faecalis influences the differentiation of murine bone marrow-derived stem cells (BMSCs) into functional DCs in the presence of the cytokines granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4). Although the viability and differentiation of DCs were not affected by E. faecalis, expression of the autophagy-related proteins ATG7, Beclin1, and LC3bI/II were significantly suppressed in an mTOR-dependent manner. Ultrastructurally, E. faecalis was identified in single-membrane vacuoles, some of which were in the process of binary fission. Bacterium-containing autophagosomes were absent within the cytoplasm. Accessory molecules (major histocompatibility complex class II [MHC-II], CD80, and CD86) and anti-inflammatory cytokine (transforming growth factor β1 [TGF-β1]) were suppressed in E. faecalis-induced DCs, while IL-1β, tumor necrosis factor alpha (TNF-α), and IL-12 levels were upregulated. When pulsed with ovalbumin (OVA), the E. faecalis-induced DCs showed reduction in CD4+ OVA-specific OT-II T cell proliferation. It is concluded that E. faecalis promotes the differentiation of bone marrow stem cells into CD11c-positive DCs with aberrant immune functions while retaining the capability of proinflammatory cytokine induction.

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Lactobacillus plantarumLG42 Isolated from Gajami Sik-Hae Inhibits Adipogenesis in 3T3-L1 Adipocyte

BioMed Research International ◽

10.1155/2013/460927 ◽

2013 ◽

Vol 2013 ◽

pp. 1-7 ◽

Cited By ~ 11

Author(s):

Jeong-Eun Park ◽

Suk-Heung Oh ◽

Youn-Soo Cha

Keyword(s):

Transcription Factors ◽

Fatty Acid ◽

Lipid Accumulation ◽

Binding Protein ◽

Peroxisome Proliferator ◽

Dependent Manner ◽

Peroxisome Proliferator Activated Receptor ◽

Fatty Acid Binding ◽

Intracellular Lipid Accumulation ◽

Glycerol 3 Phosphate Dehydrogenase

We investigated whether lactic acid bacteria isolated from gajami sik-hae (GLAB) are capable of reducing the intracellular lipid accumulation by downregulating the expression of adipogenesis-related genes in differentiated 3T3-L1 cells. The GLAB,Lactobacillus plantarumLG42, significantly decreased the intracellular triglyceride storage and the glycerol-3-phosphate dehydrogenase (GPDH) activity in a dose-dependent manner. mRNA expression of transcription factors like peroxisome proliferator-activated receptor (PPAR)γand CCAAT/enhancer-binding protein (C/EBP)αinvolved in adipogenesis was markedly decreased by the GLAB treatment. Moreover, the GLAB also decreased the expression level of adipogenic markers like adipocyte fatty acid binding protein (aP2), leptin, GPDH, and fatty acid translocase (CD36) significantly. These results suggest that the GLAB inhibits lipid accumulation in the differentiated adipocyte through downregulating the expression of adipogenic transcription factors and other specific genes involved in lipid metabolism.

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Fatty acid binding proteins shape the cellular response to activation of the glucocorticoid receptor

10.1101/2021.07.02.450968 ◽

2021 ◽

Author(s):

Bonan Liu ◽

Indu R Chandrashekaran ◽

Olga Ilyichova ◽

Damien Valour ◽

Fabien Melchiore ◽

...

Keyword(s):

Fatty Acid ◽

Glucocorticoid Receptor ◽

Cellular Response ◽

Transcriptional Activity ◽

Binding Proteins ◽

Nuclear Hormone Receptor ◽

Fatty Acid Binding Proteins ◽

Type I ◽

Dependent Manner ◽

Fatty Acid Binding

Glucocorticoids are steroid hormones that are essential for life in mammals. Therapeutically, they are some of the most cost-effective drugs for the treatment of inflammatory diseases ranging from skin rashes to COVID-19, but their use is limited by adverse effects. Glucocorticoids exert their effects via the glucocorticoid receptor, a type I nuclear hormone receptor which modulates gene expression. The transcriptional activity of some related, but nuclear restricted, type II nuclear hormone receptors can be enhanced by a family of intracellular transport proteins, the fatty acid binding proteins (FABPs). We find that the transcriptional activity of the GR can be altered by a sub-set of FABP family members dependent on the GR-ligand. The ability of some FABPs to selectively promote or limit the transcriptional activity of the GR in a ligand-dependent manner could facilitate the discovery of drugs that narrow GR activity to only the desired subset of therapeutically relevant genes.

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High-Fat Feeding in Time-Dependent Manner Affects Metabolic Routes Leading to Nervonic Acid Synthesis in NAFLD

International Journal of Molecular Sciences ◽

10.3390/ijms20153829 ◽

2019 ◽

Vol 20 (15) ◽

pp. 3829 ◽

Cited By ~ 3

Author(s):

Konstantynowicz-Nowicka ◽

Berk ◽

Chabowski ◽

Kasacka ◽

Bielawiec ◽

...

Keyword(s):

Fatty Acid Composition ◽

Fatty Acid ◽

Acid Composition ◽

Lipid Accumulation ◽

Time Dependent ◽

Nervonic Acid ◽

Dependent Manner ◽

High Fat ◽

Lipid Fractions ◽

Fat Feeding

Nonalcoholic fatty liver disease (NAFLD) is characterized by excessive lipid accumulation in the liver. The disturbances in the fatty acid composition of stored lipids are more important than the lipid species itself, which may influence the overall effect caused by these molecules. Thus, uncovering time-dependent changes in the fatty acid composition of accumulated lipid fractions after a high fat diet seems to be a new marker of NAFLD occurrence. The experiments were conducted on high fat fed Wistar rats. The blood and liver samples were collected at the end of each experimental week and used to assess the content of lipid fractions and their fatty acid composition by gas liquid chromatography. The expression of proteins from lipid metabolism pathways and of fatty acid exporting proteins were detected by Western blotting. In the same high fat feeding period, decreased de novo lipogenesis, increased β-oxidation and lipid efflux were demonstrated. The observed effects may be the first liver protective mechanisms against lipotoxicity. Nevertheless, such effects were still not sufficient to prevent the liver from proinflammatory lipid accumulation. Moreover, the changes in liver metabolic pathways caused the plasma nervonic acid concentration in sphingomyelin to decrease simultaneously with NAFLD development, which may be a steatosis occurrence prognostic marker.

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Ligustrum Japonicum fructus Induces Anti-adipogenetic and Pro-osteoblastogenic Activities in Human Bone Marrow-derived Mensencymal Stem Cells (P06-016-19)

Current Developments in Nutrition ◽

10.1093/cdn/nzz031.p06-016-19 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Author(s):

JungHwan Oh ◽

Fatih Karadeniz ◽

JungIm Lee ◽

Youngwan Seo ◽

Chang-Suk Kong

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Lipid Accumulation ◽

Osteoblast Differentiation ◽

Adipogenic Differentiation ◽

Dependent Manner ◽

Cellular Lipid ◽

Protein Levels ◽

Alp Activity ◽

Ligustrum Japonicum

Abstract Objectives Masenchymal stem cells (MSCs) have pluripotent differentiation properties that confirmed to differentiate into myocyte, adipocyte, osteoblast, neuron and chondrocyte when specific culture conditions and stimuli are applied. In bone, both adipocytes and osteoblasts are derived from bone marrow MSCs (BMSCs) and production of these cells has been reported as reciprocal processes. The bone mass disequilibrium causes osteoporosis, as a result of elevated adipogenic differentiation accompanied by reducing bone formation. Therefore, in this study the effect of Ligustrum japonicum fructus (Waxleaf privet) on the adipogenesis and osteoblast differentiation was investigated in BMSCs. Methods The fruits of L. japonicum were extracted with dichloromethane and methanol, and the combined extracts were concentrated. Differentiation of BMSCs was performed by changing the medium into adipocyte and osteoblast differentiation supplied by Promocell GmbH. The cellular lipid was stained with Oil Red O and the alkaline phosphatase (ALP) activity was measured using a colormetric assay kit (Biovision, Inc.). The relative protein levels were measured by immunoblotting assay. Results Presense of L. japonicum fructus extract (LJE) inhibited the cellular lipid accumulation in a dose-dependent manner. Consistent with the effects on lipid accumulation, the adipocyte specific genes including PPARγ, C/EBPα and SREBP1c was down regulated by treatment with LJE. Moreover, treatment with LJE enhanced osteoblast differentiation observed as increased ALP activity and upregulated the proteALP, BMP-2 and osteocalcine protein levels. Conclusions The results indicated that LJE may prevent bone loss by inhibiting adipogenesis while activating the osteogenic differentiation in BMSCs. Therefore, LJE possess the potential to be utilized as a source of nutraceutical agents against osteoporosis. Funding Sources This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP).

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Catalpol Attenuates Hepatic Steatosis by Regulating Lipid Metabolism via AMP-Activated Protein Kinase Activation

BioMed Research International ◽

10.1155/2020/6708061 ◽

2020 ◽

Vol 2020 ◽

pp. 1-12 ◽

Cited By ~ 1

Author(s):

Xiang Tian ◽

Qin Ru ◽

Qi Xiong ◽

Ruojian Wen ◽

Yong Chen

Keyword(s):

Fatty Acid ◽

Protein Kinase ◽

Hepatic Steatosis ◽

Lipid Accumulation ◽

Hepg2 Cells ◽

Fatty Acid Synthase ◽

Target Genes ◽

Dependent Manner ◽

Compound C ◽

Amp Activated Protein Kinase

The increased prevalence of nonalcoholic fatty liver disease (NAFLD), which develops from hepatic steatosis, represents a public health challenge. Catalpol, a natural component extracted from the roots of Radix Rehmanniae, has several pharmacological activities. The present study is aimed at examining whether catalpol prevents hepatic steatosis in cell and animal experiments and elucidating the possible mechanisms. HepG2 cells were treated with 300 μM palmitate (PA) and/or catalpol for 24 h in vitro, and male C57BL/6J mice fed a high-fat diet (HFD) were administered catalpol for 18 weeks in vivo. The results revealed that catalpol significantly decreased lipid accumulation in PA-treated HepG2 cells. Moreover, catalpol drastically reduced body weight and lipid accumulation in the liver, whereas it ameliorated hepatocyte steatosis in HFD-fed mice. Notably, catalpol remarkably promoted the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase. Subsequently, catalpol repressed the expressions of lipogenesis-associated genes such as sterol regulatory element-binding protein 1c and fatty acid synthase but promoted the expressions of genes associated with fatty acid β-oxidation such as peroxisome proliferator-activated receptor α together with its target genes carnitine palmitoyltransferase 1 and acyl-CoA oxidase 1 (ACOX1). However, the preincubation of the HepG2 cells with compound C (10 μM), an AMPK inhibitor, prevented catalpol-mediated beneficial effects. These findings suggest that catalpol ameliorates hepatic steatosis by suppressing lipogenesis and enhancing fatty acid β-oxidation in an AMPK-dependent manner. Therefore, catalpol has potential as a novel agent in the treatment of NAFLD.

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Euodia daniellii Hemsl. (Bee-Bee Tree) Oil Attenuates Palmitate-Induced Lipid Accumulation and Apoptosis in Hepatocytes

Pharmacology ◽

10.1159/000487892 ◽

2018 ◽

Vol 101 (5-6) ◽

pp. 298-308

Author(s):

Tae Woo Jung ◽

Sun-Young Kim ◽

Da-Som Kim ◽

Eui-Cheol Shin ◽

Yong Bae Park ◽

...

Keyword(s):

Fatty Acid ◽

Protein Kinase ◽

Saturated Fatty Acid ◽

Lipid Accumulation ◽

Caspase 3 ◽

Kinase Inhibitors ◽

Adenosine Monophosphate ◽

Protein Kinase Inhibitors ◽

Dependent Manner ◽

Protective Effects

Hepatic lipid accumulation and apoptosis is elevated in patients with non-alcoholic steatohepatitis and is closely associated with severity. Saturated fatty acid palmitate stimulates lipid accumulation and apoptosis in hepatocytes. In the present study, we examined bee-bee tree oil (BO)-mediated protective effects on palmitate-induced lipid accumulation and apoptosis in mouse primary hepatocytes. Cells were cultured in a control media or the same media containing 150 or 300 µmol/L of albumin-bound palmitate for 24 h. BO concentrations used were 0, 0.1, 0.2, or 0.5%. Palmitate induced lipid accumulation and mRNA expression of lipogenic genes such as SREBP1c and SCD1. However, BO prevented these changes. Furthermore, palmitate stimulated caspase-3 activity and decreased cell viability in the absence of BO. BO reduced palmitate-induced activation of caspase-3 and cell death in a dose-dependent manner. AMP-activated protein kinase inhibitors abolished the effects of BO. Furthermore, BO suppressed palmitate-induced c-Jun N-terminal kinase (JNK) phosphorylation through the 5' adenosine monophosphate-activated protein kinase (AMPK)-dependent pathway. In conclusion, BO attenuated palmitate-induced hepatic steatosis and apoptosis through AMPK-mediated suppression of JNK signaling. These data suggest that BO is an important determinant of saturated fatty acid-induced lipid accumulation and apoptosis, and may be an effective therapeutic strategy for treatment of obesity-mediated liver diseases.

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Ionizing radiation–induced expression of INK4a/ARF in murine bone marrow–derived stromal cell populations interferes with bone marrow homeostasis

Blood ◽

10.1182/blood-2011-06-361626 ◽

2012 ◽

Vol 119 (3) ◽

pp. 717-726 ◽

Cited By ~ 39

Author(s):

Cynthia L. Carbonneau ◽

Geneviève Despars ◽

Shanti Rojas-Sutterlin ◽

Audrey Fortin ◽

Oanh Le ◽

...

Keyword(s):

Bone Marrow ◽

Ionizing Radiation ◽

Stromal Cells ◽

Stromal Cell ◽

Cell Populations ◽

Dependent Manner ◽

Murine Bone Marrow ◽

Genetic Manipulations ◽

Residual Damage ◽

Radiation Induced

Abstract Alterations of the BM microenvironment have been shown to occur after chemoradiotherapy, during aging, and after genetic manipulations of telomere length. Nevertheless, whether BM stromal cells adopt senescent features in response to these events is unknown. In the present study, we provide evidence that exposure to ionizing radiation (IR) leads murine stromal BM cells to express senescence markers, namely senescence-associated β-galactosidase and increased p16INK4a/p19ARF expression. Long (8 weeks) after exposure of mice to IR, we observed a reduction in the number of stromal cells derived from BM aspirates, an effect that we found to be absent in irradiated Ink4a/arf-knockout mice and to be mostly independent of the CFU potential of the stroma. Such a reduction in the number of BM stromal cells was specific, because stromal cells isolated from collagenase-treated bones were not reduced after IR. Surprisingly, we found that exposure to IR leads to a cellular nonautonomous and Ink4a/arf-dependent effect on lymphopoiesis. Overall, our results reveal the distinct sensitivity of BM stromal cell populations to IR and suggest that long-term residual damage to the BM microenvironment can influence hematopoiesis in an Ink4a/arf-dependent manner.

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