Academic literature on the topic 'Monocytic lipid metabolism'
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Journal articles on the topic "Monocytic lipid metabolism"
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Nakagawa, Kiyotaka, Jean-Marc Zingg, Sharon H. Kim, Michael J. Thomas, Gregory G. Dolnikowski, Angelo Azzi, Teruo Miyazawa, and Mohsen Meydani. "Differential cellular uptake and metabolism of curcuminoids in monocytes/macrophages: regulatory effects on lipid accumulation." British Journal of Nutrition 112, no. 1 (April 11, 2014): 8–14. http://dx.doi.org/10.1017/s0007114514000567.
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We have previously shown that curcumin (CUR) may increase lipid accumulation in cultured human acute monocytic leukaemia cell line THP-1 monocytes/macrophages, but that tetrahydrocurcumin (THC), an in vivo metabolite of CUR, has no such effect. In the present study, we hypothesised that the different cellular uptake and/or metabolism of CUR and THC might be a possible explanation for the previously observed differences in their effects on lipid accumulation in THP-1 monocytes/macrophages. Chromatography with tandem MS revealed that CUR was readily taken up by THP-1 monocytes/macrophages and slowly metabolised to hexahydrocurcumin sulphate. By contrast, the uptake of THC was low. In parallel with CUR uptake, increased lipid uptake was observed in THP-1 macrophages but not with the uptake of THC or another CUR metabolite and structurally related compounds. From these results, it is possible to deduce that CUR and THC are taken up and metabolised differently in THP-1 cells, which determine their biological activity. The remarkable differential cellular uptake of CUR, relative to THC and other similar molecules, may imply that the CUR uptake into cells may occur via a transporter.
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Sang, Yongming, Raymond Rowland, and Frank Blecha. "Antiviral regulation in porcine monocytic cells at different activation states (INC8P.430)." Journal of Immunology 192, no. 1_Supplement (May 1, 2014): 187.3. http://dx.doi.org/10.4049/jimmunol.192.supp.187.3.
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Abstract Many pandemic viruses are monocytotropic, including porcine reproductive and respiratory syndrome virus (PRRSV), which directly infects subsets of macrophages and DCs and interferes in antiviral responses. To study antiviral responses in PRRSV-infected monocytic cells, we characterized inflammatory cytokine responses and genome-wide profiled signature genes to investigate response pathways in uninfected and PRRSV-infected monocytic cells at different activation states. Our findings showed suppressed interferon (IFN) production in macrophages at non-antiviral states and an arrest of lipid metabolic pathways in macrophages at antiviral states. Importantly, porcine monocytic cells at different activation states were susceptible to PRRSV and responded to viral infection differently. Based on gene ontology analysis, two approaches were used: 1) pharmaceutical modulation of cellular lipid metabolism and 2) in situ PRRSV replication-competent expression of IFN-α; both approaches significantly suppressed exogenous viral infection in monocytic cells. In particular, the engineered IFN-expressing PRRSV strain eliminated exogenous virus infection and sustained cell viability at 4 days post infection in macrophages. These findings suggest an intricate interaction of viral infection with activation status of porcine monocytic cells. An understanding and integration of antiviral infection with activation status of monocytic cells may provide a means of potentiating antiviral immunity.
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Thomas, A. W., N. A. Davies, H. Moir, L. Watkeys, J. S. Ruffino, S. A. Isa, L. R. Butcher, M. G. Hughes, K. Morris, and R. Webb. "Exercise-associated generation of PPARγ ligands activates PPARγ signaling events and upregulates genes related to lipid metabolism." Journal of Applied Physiology 112, no. 5 (March 1, 2012): 806–15. http://dx.doi.org/10.1152/japplphysiol.00864.2011.
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The aim of the present study was to test the hypotheses that exercise is associated with generation of peroxisome proliferator-activated receptor-γ (PPARγ) ligands in the plasma and that this may activate PPARγ signaling within circulating monocytes, thus providing a mechanism to underpin the exercise-induced antiatherogenic benefits observed in previous studies. A cohort of healthy individuals undertook an 8-wk exercise-training program; samples were obtained before (Pre) and after (Post) standardized submaximal exercise bouts (45 min of cycling at 70% of maximal O2 uptake, determined at baseline) at weeks 0, 4, and 8. Addition of plasma samples to PPARγ response element (PPRE)-luciferase reporter gene assays showed increased PPARγ activity following standardized exercise bouts (Post/Pre = 1.23 ± 0.10 at week 0, P < 0.05), suggesting that PPARγ ligands were generated during exercise. However, increases in PPARγ/PPRE-luciferase activity in response to the same standardized exercise bout were blunted during the training program (Post/Pre = 1.18 ± 0.14 and 1.10 ± 0.10 at weeks 4 and 8, respectively, P > 0.05 for both), suggesting that the relative intensity of the exercise may affect PPARγ ligand generation. In untrained individuals, specific transient increases in monocyte expression of PPARγ-regulated genes were observed within 1.5–3 h of exercise (1.7 ± 0.4, 2.6 ± 0.4, and 1.4 ± 0.1 fold for CD36, liver X receptor-α, and ATP-binding cassette subfamily A member 1, respectively, P < 0.05), with expression returning to basal levels within 24 h. In contrast, by the end of the exercise program, expression at the protein level of PPARγ target genes had undergone sustained increases that were not associated with an individual exercise bout (e.g., week 8 Pre/ week 0 Pre = 2.79 ± 0.61 for CD36, P < 0.05). Exercise is known to upregulate PPARγ-controlled genes to induce beneficial effects in skeletal muscle (e.g., mitochondrial biogenesis and aerobic respiration). We suggest that parallel exercise-induced benefits may occur in monocytes, as monocyte PPARγ activation has been linked to beneficial antidiabetic effects (e.g., exercise-induced upregulation of monocytic PPARγ-controlled genes is associated with reverse cholesterol transport and anti-inflammatory effects). Thus, exercise-triggered monocyte PPARγ activation may constitute an additional rationale for prescribing exercise to type 2 diabetes patients.
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Al-Roub, Areej, Nadeem Akhter, Amnah Al-Sayyar, Ajit Wilson, Reeby Thomas, Shihab Kochumon, Fatema Al-Rashed, Fahd Al-Mulla, Sardar Sindhu, and Rasheed Ahmad. "Short Chain Fatty Acid Acetate Increases TNFα-Induced MCP-1 Production in Monocytic Cells via ACSL1/MAPK/NF-κB Axis." International Journal of Molecular Sciences 22, no. 14 (July 19, 2021): 7683. http://dx.doi.org/10.3390/ijms22147683.
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Short-chain fatty acid (SCFA) acetate, a byproduct of dietary fiber metabolism by gut bacteria, has multiple immunomodulatory functions. The anti-inflammatory role of acetate is well documented; however, its effect on monocyte chemoattractant protein-1 (MCP-1) production is unknown. Similarly, the comparative effect of SCFA on MCP-1 expression in monocytes and macrophages remains unclear. We investigated whether acetate modulates TNFα-mediated MCP-1/CCL2 production in monocytes/macrophages and, if so, by which mechanism(s). Monocytic cells were exposed to acetate with/without TNFα for 24 h, and MCP-1 expression was measured. Monocytes treated with acetate in combination with TNFα resulted in significantly greater MCP-1 production compared to TNFα treatment alone, indicating a synergistic effect. On the contrary, treatment with acetate in combination with TNFα suppressed MCP-1 production in macrophages. The synergistic upregulation of MCP-1 was mediated through the activation of long-chain fatty acyl-CoA synthetase 1 (ACSL1). However, the inhibition of other bioactive lipid enzymes [carnitine palmitoyltransferase I (CPT I) or serine palmitoyltransferase (SPT)] did not affect this synergy. Moreover, MCP-1 expression was significantly reduced by the inhibition of p38 MAPK, ERK1/2, and NF-κB signaling. The inhibition of ACSL1 attenuated the acetate/TNFα-mediated phosphorylation of p38 MAPK, ERK1/2, and NF-κB. Increased NF-κB/AP-1 activity, resulting from acetate/TNFα co-stimulation, was decreased by ACSL1 inhibition. In conclusion, this study demonstrates the proinflammatory effects of acetate on TNF-α-mediated MCP-1 production via the ACSL1/MAPK/NF-κB axis in monocytic cells, while a paradoxical effect was observed in THP-1-derived macrophages.
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Todd, R. F., P. A. Alvarez, D. A. Brott, and D. Y. Liu. "Bacterial lipopolysaccharide, phorbol myristate acetate, and muramyl dipeptide stimulate the expression of a human monocyte surface antigen, Mo3e." Journal of Immunology 135, no. 6 (December 1, 1985): 3869–77. http://dx.doi.org/10.4049/jimmunol.135.6.3869.
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Abstract Exposure of mononuclear phagocytes to bacterial lipopolysaccharide (LPS), phorbol myristate acetate (PMA), or muramyl dipeptide (MDP) is known to stimulate a variety of cellular activities that include increases in phagocytosis, oxidative metabolism, synthesis and secretion of monokines, and cytotoxicity of microbes and tumor cells. We now report that culture of human peripheral blood monocytes in medium containing LPS, phorbol compounds, or MDP also results in the acquired expression of a plasma membrane antigen. Mo3e, as identified by a murine monoclonal antibody. Mo3e is barely detectable (by immunofluorescence flow cytometry) on freshly isolated monocytes, but is expressed in high antigen density after exposure of cells to E. coli, Salmonella minnesota, or Serratia marcescens LPS (at concentrations exceeding 0.1 ng/ml), PMA (and other biologically active phorbol compounds) (0.5 to 1 X 10(-8) M), or MDP (0.01 to 1 X 10(-6) M). Mo3e expression stimulated by LPS is prevented by pretreatment of LPS with polymyxin B, suggesting that the lipid A portion of LPS is responsible for Mo3e induction (polymyxin B has no effect on Mo3e expression stimulated by PMA or MDP). Culture of monocytes in medium containing protein synthesis inhibitors (or at 4 degrees C) blocks the acquisition of Mo3e. Recombinant IFN-gamma, which is also known to "activate" mononuclear phagocytes, does not stimulate Mo3e expression, although both LPS and IFN induce enhanced expression of monocyte Ia antigen. Analogous to their stimulatory effect on monocytes, LPS and PMA induce Mo3e expression by the human monocytic cell line, U-937. On the basis of these observations, Mo3e may represent an immunologic marker for monocyte activation stimulated in vitro by LPS, PMA (and related compounds), and MDP.
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BENGTSSON, Sara H. M., Katja MADEYSKI-BENGTSON, Jeanette NILSSON, and Gunnar BJURSELL. "Transcriptional regulation of the human carboxyl ester lipase gene in THP-1 monocytes: an E-box required for activation binds upstream stimulatory factors 1 and 2." Biochemical Journal 365, no. 2 (July 15, 2002): 481–88. http://dx.doi.org/10.1042/bj20020223.
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The bile salt-stimulated carboxyl ester lipase (CEL) is important for the digestion and absorption of dietary lipids, and is expressed at high levels by the exocrine pancreas and the lactating mammary gland. However, the presence of CEL in human plasma suggests that the role of CEL in lipid metabolism may stretch beyond its function in the intestinal lumen, and possibly include interactions with cholesterol and oxidized lipoproteins to modulate the progression of atherosclerosis. We have used the CEL-expressing human monocytic cell line THP-1 to investigate the transcriptional regulation of the human CEL in monocytes. Analyses of the promoter region revealed that an E-box located at −47/−52 is necessary for CEL expression. Point mutations in the E-box almost completely abolish the transcriptional activity. Electrophoretic mobility-shift assay analyses reveal that the E-box binds the upstream stimulatory factors 1 and 2, and the binding of an upstream stimulatory factor-containing complex in THP-1 cells also requires the presence of a putative nuclear receptor-binding site at −60/−66. Furthermore, we demonstrate that the E-box is also necessary for CEL expression in the pancreas and the mammary gland, although there are tissue-specific requirements for additional activating elements.
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Jin, Linhua, Yoko Tabe, Marina Konopleva, Michael Andreeff, Akimichi Ohsaka, and Takashi Miida. "Bone Marrow-Derived Adipocytes Promote Differentiation, Proliferation and Survival of Acute Monoblastic Leukemia Cells." Blood 118, no. 21 (November 18, 2011): 1501. http://dx.doi.org/10.1182/blood.v118.21.1501.1501.
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Abstract Abstract 1501 Acute monoblastic leukemia occurs most commonly in young individuals, whereas acute monocytic leukemia is common in adults (WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, 2008). Adipocytes are the prevalent stromal cell type in adult bone marrow (BM) and play an important role in the leukemic bone marrow microenvironment (Tabe et al., Blood 2004 103: 1815–22). BM stromal cells (MSCs) from elderly subjects have a reduced capacity to differentiate into osteoblasts and an increased capacity to differentiate into adipocytes, which leads to progressive accumulation of fat in the BM space with increasing age. In this study, we examined whether BM-derived adipocytes participate in the molecular events associated with proliferation, differentiation and apoptosis of monoblastic leukemia cells. To this end, we performed gene expression microarray analysis of 339 genes associated with lipid metabolism (GeneSQUARE, Kurabo, Japan) using RNA from monoblastic leukemia cell line U937 co-cultured with MSC or MSC-derived adipocytes. Five genes were upregulated (>2.0 fold) and 2 genes down-regulated in U937 cells co-cultured with adipocytes compared to U937 cultured alone. The up-regulated genes included monocyte/macrophage differentiation specific genes, such as scavenger receptor CD36, adipsin or fatty acid binding protein 4 (FABP4). CD36 and FABP4 are classical target genes of PPARγ which was also upregulated in U937 co-cultured with adipocytes. Upregulation of the inflammation-related haptoglobin gene was observed in U937 cells co-cultured with either adipocytes or MSC. These findings were confirmed by quantitative RT-PCR assay with concordant results. Down-regulated genes included monocyte chemoattractant protein-1 (MCP-1) (0.1 fold) and glycolytic enzyme hexokinase 2 (0.4 fold). In turn, U937 cells co-cultured with premature or mature adipocytes accumulated in G2 cell cycle phase compared to U937 cultured alone or co-cultured with MSC (% G2/M-phase fraction; U937 cultured alone, 14.6, co-culture with MSC 25.1, co-culture with preadipocyte 32.0, with mature adipocyte 31.9) and were protected from spontaneous cell death under serum-starved conditions (% subG1 fraction: U937 cultured alone 23.9%, co-cultured with MSC 15.7%, with preadipocytes 3.9% and with mature adipocytes 11.6%). In summary, results suggest that BM adipocytes, abundant in adult BM space, promote monocytic differentiation, proliferation and survival of monoblastic leukemia cells. We propose that these cells represent an essential component of the BM microenvironment that contributes to malignant phenotypes of adults with monocytic leukemia. Disclosures: No relevant conflicts of interest to declare.
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Strauss, Laura, Jessica D. Weaver, Rinku Pal, John Asara, Nikolaos Patsoukis, and Vassiliki A. Boussiotis. "Metabolic Reprogramming of Myeloid Cells in Response to Factors of "Emergency" Myelopoiesis By Myeloid-Specific PD-1 Ablation, Regulates Myeloid Lineage Fate Commitment and Anti-Tumor Immunity." Blood 132, Supplement 1 (November 29, 2018): 14. http://dx.doi.org/10.1182/blood-2018-99-117438.
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Abstract PD-1 is a T cell inhibitor for which blocking agents have achieved success as anti-cancer therapeutics. The current view is that cancer limits host immune responses by upregulating PD-L1 in the tumor microenvironment (TME) thereby causing PD-1 ligation and inactivation of CD8+ Teff cells. However, PD-L1 expression in the TME does not always correlate with therapeutic response. Thus, the mechanism(s) by which PD-1 blockade reverses compromised anti-tumor immunity are poorly understood. The rapid increase in hematopoietic cell output that occurs in response to immunologic stress is known as emergency myelopoiesis. Low-level stimulation by cancer-generated factors induces modest but continuous expansion of myeloid progenitors (MP) (common myeloid progenitors (CMP) and granulocyte/macrophage progenitors (GMP)) albeit with hindered differentiation, leading to output of tumor-promoting myeloid-derived suppressor cells (MDSCs). We determined that myeloid cells expanding during cancer-driven emergency myelopoiesis in tumor-bearing mice express PD-1 and PD-L1. Using PD-1 KO mice we found that PD-1 deletion prevented the accumulation of GMP and stimulated the output of Ly6Chi effector monocytes, macrophages and dendritic cells (DC). To determine whether these outcomes were mediated by a myeloid-intrinsic impact of PD-1 ablation or by the effects of PD-1neg T cells on myeloid cells, we generated mice with conditional targeting of the Pdcd1 gene (PD-1f/f) and selectively eliminated PD-1 in myeloid cells (PD-1f/fLysMcre) or T cells (PD-1f/fCD4cre). Myeloid-specific, but not T cell-specific PD-1 ablation, prevented the accumulation of GMP while promoting the output of effector-like myeloid cells expressing CD80, CD86, CD16/32 (FcRII/III) and CD88 (C5aR). Myeloid cells with PD-1 ablation had elevated expression of IRF8 that drives monocyte and DC differentiation and decreased expression of the MDSC hallmark markers IL-4R, CD206, ARG1 and CD38. Nutrient utilization has a decisive role on the fate of hematopoietic progenitors (HP) and MP. Stemness and pluripotency are regulated by maintenance of glycolysis whereas switch to mitochondrial metabolism is associated with differentiation. To examine whether PD-1 ablation affected these metabolic proceces, bone marrow (BM) from PD-1f/f and PD-1f/fLysMcre mice was cultured with G-CSF/GM-CSF/IL-6, key drivers of emergency myelopoiesis. MP differentiation was documented by decrease of Linneg and increase of Linpos cells, which was more prominent in PD-1f/fLysMcre BM cultures. This coincided with increase of CD45+CD11b+ and dominance of Ly6C+ monocytic cells consistent with a cell-intrinsic mechanism of monocytic lineage commitment. PD-1f/fLysMcre MP had elevated mTORC1, Erk1/2 and Stat1 activation, and enhanced glucose uptake and mitochondrial biogenesis. Bioenergetics studies showed robust development of a mitochondrial-dominant profile, consistent with metabolism-driven enhanced differentiation of MP. Mass spectrometry revealed enhanced intermediates of glycolysis, PPP and TCA cycle, but the most prominent difference was the increased cholesterol. Because mTORC1 signaling, which was enhanced in PD-1f/fLysMcre MP, activates de novo lipid and cholesterol synthesis via SREBP1, we examined the mevalonate pathway of cholesterol synthesis. mRNA for genes mediating cholesterol synthesis and uptake was increased whereas mRNA for genes mediating cholesterol metabolism was decreased. Cholesterol induces a proinflammatory program in myeloid cells, drives differentiation of monocytes, macrophages and DC and promotes antigen-presenting function. We examined how such changes in myeloid cells might affect the function of T cells, which are key anti-tumor mediators. Compared to tumor-bearing PD-1f/f mice, PD-1f/fLysMcre tumor-bearers had no quantitative T cell differences but had an increase in IFNγ- IL-17-, and IL-10-expressing CD8+ Teff-mem and IL-2-expressing Tcentral-mem cells, consistent with superior functionality. These changes correlated with enhanced anti-tumor protection despite preserved PD-1 expression in T cells. Our findings reveal a previously unidentified role of PD-1 in metabolism-driven myeloid cell lineage fate commitment and differentiation and suggest that switch to effector myeloid cells might be a key mechanism by which PD-1 blockade mediates systemic anti-tumor immunity. Disclosures No relevant conflicts of interest to declare.
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Spinelli, Sherry L., Stephen J. Pollock, Thomas I. Murant, Jamie J. O’Brien, Neil Blumberg, Charles W. Francis, Mark B. Taubman, Denise M. Ray, and Richard P. Phipps. "Peroxisome proliferator-activated receptor γ and retinoid X receptor transcription factors are released from activated human platelets and shed in microparticles." Thrombosis and Haemostasis 99, no. 01 (2008): 86–95. http://dx.doi.org/10.1160/th07-05-0328.
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SummaryPeroxisome proliferator-activated receptor γ (PPARγ) and its ligands are important regulators of lipid metabolism, inflammation, and diabetes. We previously demonstrated that anucleate human platelets express the transcription factor PPARγ and that PPARγ ligands blunt platelet activation. To further understand the nature of PPARγ in platelets, we determined the platelet PPARγ isoform(s) and investigated the fate of PPARγ following platelet activation. Our studies demonstrated that human platelets contain only the PPARγ1 isoform and after activation with thrombin, TRAP, ADP or collagen PPARγ is released from internal stores. PPARγ release was blocked by a cytoskeleton inhibitor, Latrunculin A. Platelet-released PPARγ was complexed with the retinoid X receptor (RXR) and retained its ability to bind DNA. Interestingly, the released PPARγ and RXR were microparticle associated and the released PPARγ/RXR complex retained DNA-binding ability. Additionally, a monocytic cell line, THP-1, is capable of internalizing PMPs. Further investigation following treatment of these cells with the PPARγ agonist, rosiglitazone and PMPs revealed a possible transcellular mechanism to attenuate THP-1 activation. These new findings are the first to demonstrate transcription factor release from platelets, revealing the complex spectrum of proteins expressed and expelled from platelets, and suggests that platelet PPARγ has an undiscovered role in human biology.
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Tabe, Yoko, Masako Harada, Yuka Miyamae, Kaoru Mogushi, Saiko Kazuno, Tsutomu Fujimura, Hiromichi Matsushita, et al. "Bone Marrow Adipocyte-Derived Free Fatty Acids Induce Gene Signature Linking Transcription with Metabolic Changes That Contribute to Survival of Acute Monocytic Leukemia Cells." Blood 124, no. 21 (December 6, 2014): 1013. http://dx.doi.org/10.1182/blood.v124.21.1013.1013.
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Abstract Adipocytes are the prevalent stromal cell type in adult bone marrows (BM). With increasing age, BM stroma-resident mesenchymal stem cells (MSCs), increase their capacity to differentiate into adipocytes, which leads to the progressive accumulation of fat in the BM space. It is conceivable that the increased BM adipocyte content promotes leukemogenesis and negatively affects responsiveness to chemotherapy. We previously reported that free fatty acids (FFAs) promote the metabolic shift from pyruvate oxidation to fatty acid oxidation (FAO), which causes uncoupling of mitochondrial oxidative phosphorylation and promotes leukemia cell survival (Samudio, J Clin Invest. 2010). We further demonstrated the prominent antiapoptotic effects of BM-derived adipocytes co-cultured with cells from acute monocytic leukemia (AMoL), a poor-prognosis subtype of AML (Tabe ASH. 2013). Proteomic analysis with isobaric tags for relative and absolute quantification (iTRAQ) showed upregulation of protein folding pathways which increases the expression of antiapoptotic chaperone proteins HSP70 and HSP90, of integrin-mediated cell adhesion and migration pathways and downregulation of oxidative phosphorylation along with repression of cytochrome c.Metacore gene ontology (GO) analysis identified NF-kB, c-Jun, SP1, AP-1, and HMG as the potent relevant transcription factors that closely interact with and activate chaperone proteins, chromatin, and gene transcription. In this study, we characterized a gene signature linking transcription with metabolic changes that contribute to AMoL cell survival under conditions mimicking aging BM with prevalent adipocytes. We confirmed the antiapoptotic role of FFAs produced by the primary BM MSC-derived adipocytes via pharmacologic inhibition of FAO by etomoxir (EX), which inhibits fatty acid entry into the mitochondria. EX (50mM) treatment reversed the prosurvival effects of adipocytes on serum-starved U937 monoblast cells (% Annexin V, -/+ EX: mono-culture, 30.1±9.0 / 31.5±4.6; co-culture with adipocytes, 8.9±2.1 / 29.6±9.2; P=0.02). To assess the molecular links between metabolic pathways and gene expression triggered by BM adipocytes, we performed RNA-seq transcriptome analysis with a next generation sequencer system HiSeq1500 (Illumina) using TopHat software for alignment and Cufflinks software for identifying differential gene expression. RNA-Seq detected upregulation of 21 genes in U937 cells after co-culture with BM-derived adipocytes (false discovery rate, <0.05). Specifically, 10 of these upregulated genes were significantly decreased by EX treatment, including transcription factor–activating PPARg2 promoter KLF9, co-chaperone immunophilin protein FKBP5, chemokine CXCL12 receptor CXCR4, receptor tyrosine kinase FLT3, PI3K negative regulator PIK3IP1, and immunosuppressive transcriptional regulator TSC22D3. GO pathway analysis further revealed that co-culture with adipocytes induced upregulation of antioxidant thioredoxin peroxidase activity, which was reversed by EX. Together with the iTRAQ GO results, the antioxidative chaperone proteins might play critical roles in regulation of FAO with repression of oxidative phosphorylation in AMoL cells in adipocytes abundant BM. DNA array (GeneSQUARE) analysis and quantitative RT-PCR detected upregulation of fatty acid binding protein 4 (FABP4), scavenger receptor CD36, nuclear receptor PPARG, and antiapoptotic Bcl-2 in U937 cells co-cultured with adipocytes. It is known that FFAs, the ligand of nuclear receptor PPARγ, activate PPARγ and promote FFA uptake through transcriptional induction of CD36 and FABP4 in monocytic cells. EX treatment, which blocks the entry of fatty acids into the mitochondria, induced prominent elevation of FABP4 in U937 cells co-cultured with adipocytes. These results indicate that the FABP4-mediated internalization and ligation of fatty acids to PPARγ facilitates transcriptional activation. From the transcriptome analysis and the mitochondrial uncoupling metabolic changes, we conclude that the survival of AMoL cells depends on the cooperative interactions between lipid metabolism and transcriptional activation of factors associated with chaperones, chemokines, and integrins. Strategies targeting FAO warrant further exploration in patients with monocytic leukemia, which is highly dependent on altered lipid metabolism. Disclosures No relevant conflicts of interest to declare.
Dissertations / Theses on the topic "Monocytic lipid metabolism"
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Junior, Elbio Leiguez. "Estudo dos fatores envolvidos na formação de corpúsculos lipídicos, induzido por uma fosfolipase A2, isolada do veneno de serpente: síntese e metabolismo de lipídeos." Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/42/42133/tde-09062015-154735/.
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Os venenos de serpentes contêm concentrações elevadas de fosfolipases A2 secretadas (sFLA2), que apresentam homologia com as FLA2s de mamíferos, cujos níveis estão aumentados em doenças inflamatórias. Neste estudo, investigou-se a ativação e a expressão de fatores envolvidos na formação de corpúsculos lipídicos (CLs) em células fagociticas e o papel desses fatores na resposta imune inata, induzida pela MT-III, uma sFLA2s de veneno. A MT-III induziu aumento dos níveis de triacilglicerol, colesterol e lisofosfolipideos e a ativação e expressão dos fatores PPAR-g, PPAR-d/b, SREBP2 e do CD36. Sob estimulo da MT-III, o receptor PPAR-b/d, as enzimas DGAT, ACAT e FAS foram relevantes para a formação de CLs e para a expressão da PLIN2. O CD36 participa da expressão da COX-2, sem modificar a liberação de PGE2. O TLR2 e a MyD88 foram essenciais para a formação de CLs e síntese da IL-1b e IL-10. Ainda, o TLR2 foi relevante para a liberação de PGE2, PGD2 e LTB4, enquanto MyD88 foi fundamental somente para a liberação de PGE2 e expressão da PLIN2, induzidas pela MT-III.Snake venoms contain high concentrations of secreted phospholipase A2 (sPLA2) with homology to mammalian PLA2s, whose levels are elevated in inflammatory diseases. In this study, we investigated activation and expression of factors involved in lipid droplets formation (LDs) and participation that factors in the innate immune response induced by MT-III, sPLA2s from snake venom, in phagocytic cells. MT-III induced increase of triacylglycerol, cholesterol and lysophospholipids levels and activation and expression of factors PPAR-g, PPAR-d/b, SREBP2 and CD36. PPAR-b/d receptor, DGAT, ACAT and FAS enzymes were relevant to LDs formation and critical to PLIN2 expression induced by MT-III. CD36 participates in COX-2 expression without modifying PGE2 release stimulated by MT-III. TLR2 and MyD88 were essential to LDs formation and IL-1b and IL-10 synthesis stimulated by MT-III. Moreover, TLR2 was relevant to PGE2, PGD2 and LTB4 biosynthesis, while MyD88 is essential only for PGE2 release and PLIN2 expression induced by MT-III.
Book chapters on the topic "Monocytic lipid metabolism"
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Tremoli, Elena, Susanna Colli, Mariagrazia Lalli, Sonia Eligini, Paola Maderna, Franco Pazzucconi, Patrizia Risé, and Claudio Galli. "Administration of N-3 Fatty Acids to Hypertriglyceridemic Patients Reduces Monocyte Tissue Factor Activity." In Drugs Affecting Lipid Metabolism, 689–96. Dordrecht: Springer Netherlands, 1996. http://dx.doi.org/10.1007/978-94-009-0311-1_81.
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Yukawa, S., A. Hibino, T. Maeda, H. Nomoto, and I. Nishide. "Effect of Vitamin E on Metabolism of Uremic Low Density Lipoproteins in Human Monocyte-Derived Macrophage." In Lipid-Soluble Antioxidants: Biochemistry and Clinical Applications, 85–91. Basel: Birkhäuser Basel, 1992. http://dx.doi.org/10.1007/978-3-0348-7432-8_8.
Full textConference papers on the topic "Monocytic lipid metabolism"
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Schaub, R. G., and F. P. Bell. "LIPID ACCUMULATION AND METABOLISM IN CARRAGEENAN-INDUCED GRANULOMAS COMPARED TO BLOOD MONOCYTES AND THE AORTA." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643410.
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Arteries undergoing atherogenic change show an increase in cholesteryl esterifying activity by acylCoA:cholesterol acetyl-transferase (ACAT) and a progressive accumulation of cholesterol esters within monocyte derived foam cells. The study of these factors, however, is limited by the necessity of obtaining artery tissues for analysis. In this study, an in vivo model (Am J Path 118:134 and 120:391, 1985) which permits the analysis of foam cell development without requiring collection of aortas was examined in more detail. New Zealand rabbits (6 each) were either maintained on a 1% cholesterol/peanut oil diet (HD) or a regular chow diet (RD) for 2 weeks after which each had 15 ml of a 1% carra-geenan gel (Marine Colloids) injected subcutaneously into the mid-abdominal area. The rabbits were maintained on their respective diets for an additional 4 weeks. At sacrifice, blood was collected for both serum and monocyte isolation. Granulomas and aortic arches were also excised. Tissues were assayed for lipid accumulation and metabolism. Electron and light microscopy was also performed on immersion fixed (1% glutaraldehyde) granuloma tissue. Granulomas of HD rabbits were pale yellow and averaged 36 grams, while RD granulomas were a pale red and averaged 11 grams (p less than 0.05). RD granulomas did not stain with oil red 0. HD granulomas had homogenous oil red 0 staining which indicated lipid accumulation. Both RD and HD granulomas had large numbers of macrophages. RD macrophages accumulated follicular carrageenan, but not lipid. In HD granulomas, foam cell development was observed. Granuloma lipid content and metabolism paralleled the aorta and blood monocytes. The HD tissue had increased ACAT activity and lipid composition changes indicative of atherosclerosis. RD granulomas had no elevation of lipid content or ACAT activity. The results suggest that the carrageenan-induced granulomas provides a useful model for studying the biochemical and morphologic changes characteristic of aortic monocyte-derived foam cells and the early arterial atherosclerotic process.