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histone deacetylase macrophage

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https://www.readbyqxmd.com/read/29137331/hdac-inhibitors-enhance-the-immunotherapy-response-of-melanoma-cells
#1
Laurence Booth, Jane L Roberts, Andrew Poklepovic, John Kirkwood, Paul Dent
We focused on the ability of the pan-histone deacetylase (HDAC) inhibitors AR42 and sodium valproate to alter the immunogenicity of melanoma cells. Treatment of melanoma cells with HDAC inhibitors rapidly reduced the expression of multiple HDAC proteins as well as the levels of PD-L1, PD-L2 and ODC, and increased expression of MHCA. In a cell-specific fashion, melanoma isolates released the immunogenic protein HMGB1 into the extracellular environment. Very similar data were obtained in ovarian and H&NSCC PDX isolates, and in established tumor cell lines from the lung and kidney...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29058362/the-ketone-body-metabolite-%C3%AE-hydroxybutyrate-induces-an-antidepression-associated-ramification-of-microglia-via-hdacs-inhibition-triggered-akt-small-rhogtpase-activation
#2
Chao Huang, Peng Wang, Xing Xu, Yaru Zhang, Yu Gong, Wenfeng Hu, Minhui Gao, Yue Wu, Yong Ling, Xi Zhao, Yibin Qin, Rongrong Yang, Wei Zhang
Direct induction of macrophage ramification has been shown to promote an alternative (M2) polarization, suggesting that the ramified morphology may determine the function of immune cells. The ketone body metabolite β-hydroxybutyrate (BHB) elevated in conditions including fasting and low-carbohydrate ketogenic diet (KD) can reduce neuroinflammation. However, how exactly BHB impacts microglia remains unclear. We report that BHB as well as its producing stimuli fasting and KD induced obvious ramifications of murine microglia in basal and inflammatory conditions in a reversible manner, and these ramifications were accompanied with microglial profile toward M2 polarization and phagocytosis...
October 23, 2017: Glia
https://www.readbyqxmd.com/read/28972001/the-metabolic-and-proliferative-state-of-vascular-adventitial-fibroblasts-in-pulmonary-hypertension-is-regulated-through-a-mir-124-ptbp1-pkm-axis
#3
Hui Zhang, Daren Wang, Min Li, Lydie Plecitá-Hlavatá, Angelo D'Alessandro, Jan Tauber, Suzette Riddle, Sushil Kumar, Amanda R Flockton, B Alexandre McKeon, Maria G Frid, Julie A Reisz, Paola Caruso, Karim C El Kasmi, Petr Ježek, Nicholas W Morrell, Cheng-Jun Hu, Kurt R Stenmark
Background -An emerging "metabolic theory" of pulmonary hypertension (PH) suggests that cellular and mitochondrial metabolic dysfunction underlies the pathology of this disease. We and others have previously demonstrated the existence of hyper-proliferative, apoptosis-resistant, pro-inflammatory adventitial fibroblasts from human and bovine hypertensive pulmonary arterial walls (PH-Fibs) exhibit constitutive reprogramming of glycolytic and mitochondrial metabolism, accompanied by an increased ratio of glucose catabolism through glycolysis versus the TCA cycle...
September 26, 2017: Circulation
https://www.readbyqxmd.com/read/28968979/mir-122-socs1-jak2-axis-regulates-allergic-inflammation-and-allergic-inflammation-promoted-cellular-interactions
#4
Kyeonga Noh, Misun Kim, Youngmi Kim, Hanearl Kim, Hyuna Kim, Jaehwan Byun, Yeongseo Park, Hansoo Lee, Yun Sil Lee, Jongseon Choe, Young Myeong Kim, Dooil Jeoung
The regulatory role of suppressor of cytokine signaling 1 (SOCS1) in inflammation has been reported. However, its role in allergic inflammation has not been previously reported. SOCS1 mediated in vitro and in vivo allergic inflammation. Histone deacetylase-3 (HDAC3), a mediator of allergic inflammation, interacted with SOCS1, and miR-384 inhibitor, a positive regulator of HDAC3, induced features of allergic inflammation in an SOCS1-dependent manner. miRNA array analysis showed that the expression of miR-122 was decreased by antigen-stimulation...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28966618/sirt1-adenosine-monophosphate-activated-protein-kinase-%C3%AE-signaling-enhances-macrophage-polarization-to-an-anti-inflammatory-phenotype-in-rheumatoid-arthritis
#5
So Youn Park, Sung Won Lee, Sang Yeob Lee, Ki Whan Hong, Sun Sik Bae, Koanhoi Kim, Chi Dae Kim
Macrophages are crucially involved in the pathogenesis of rheumatoid arthritis (RA). Macrophages of the M1 phenotype act as pro-inflammatory mediators in synovium, whereas those of the M2 phenotype suppress inflammation and promote tissue repair. SIRT1 is a class 3 histone deacetylase with anti-inflammatory characteristics. However, the role played by SIRT1 in macrophage polarization has not been defined in RA. We investigated whether SIRT1 exerts anti-inflammatory effects by modulating M1/M2 polarization in macrophages from RA patients...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28894448/sirtuin-2-deficiency-increases-bacterial-phagocytosis-by-macrophages-and-protects-from-chronic-staphylococcal-infection
#6
Eleonora Ciarlo, Tytti Heinonen, Charlotte Théroude, Jacobus Herderschee, Matteo Mombelli, Jérôme Lugrin, Marc Pfefferlé, Beatrice Tyrrell, Sarah Lensch, Hans Acha-Orbea, Didier Le Roy, Johan Auwerx, Thierry Roger
Sirtuin 2 (SIRT2) is one of the seven members of the family of NAD(+)-dependent histone deacetylases. Sirtuins target histones and non-histone proteins according to their subcellular localization, influencing various biological processes. SIRT2 resides mainly in the cytoplasm and regulates cytoskeleton dynamics, cell cycle, and metabolic pathways. As such, SIRT2 has been implicated in the pathogenesis of neurodegenerative, metabolic, oncologic, and chronic inflammatory disorders. This motivated the development of SIRT2-directed therapies for clinical purposes...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28881218/downregulated-expression-of-mir-223-promotes-toll-like-receptor-activated-inflammatory-responses-in-macrophages-by-targeting-rhob
#7
Ningjie Zhang, Liyao Fu, Yanhong Bu, Yao Yao, Yongjun Wang
Toll-like receptors (TLRs) induced-inflammatory response must be tightly regulated to avoid impairment in host itself. Numerous factors have been identified in regulation of TLR-triggered inflammatory response. Among these, microRNAs (miRNAs) are small non-coding RNA molecules which have got much attention. MiR-223, which highly expresses in myeloid cells of the bone marrow, has reported to participate in kinds of inflammatory responses by targeting inflammasome sensor-NLRP3 to repress production of IL-6 and IL-1β, and thus attenuate inflammatory response...
November 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28855441/microrna-182-promotes-lipoprotein-lipase-expression-and-atherogenesisby-targeting-histone-deacetylase-9-in-apolipoprotein-e-knockout-mice
#8
Hai-Peng Cheng, Duo Gong, Zhen-Wang Zhao, Ping-Ping He, Xiao-Hua Yu, Qiong Ye, Chong Huang, Xin Zhang, Ling-Yan Chen, Wei Xie, Min Zhang, Liang Li, Xiao-Dan Xia, Xin-Ping Ouyang, Yu-Lin Tan, Zong-Bao Wang, Guo-Ping Tian, Xi-Long Zheng, Wei-Dong Yin, Chao-Ke Tang
BACKGROUND: Lipoprotein lipase (LPL) expressed in macrophages plays an important role in promoting the development of atherosclerosis or atherogenesis. MicroRNA-182 (miR-182) is involved in the regulation of lipid metabolism and inflammation. However, it remains unclear how miR-182 regulates LPL and atherogenesis.Methods and Results:Using bioinformatics analyses and a dual-luciferase reporter assay, we identified histone deacetylase 9 (HDAC9) as a target gene of miR-182. Moreover, miR-182 upregulated LPL expression by directly targetingHDAC9in THP-1 macrophages...
August 29, 2017: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/28832971/class-i-histone-deacetylase-inhibition-improves-pancreatitis-outcome-by-limiting-leukocyte-recruitment-and-acinar-to-ductal-metaplasia
#9
Marta Bombardo, Enrica Saponara, Ermanno Malagola, Rong Chen, Gitta M Seleznik, Cecile Haumaitre, Evans Quilichini, Anja Zabel, Theresia Reding, Rolf Graf, Sabrina Sonda
BACKGROUND AND PURPOSE: Pancreatitis is a common inflammation of the pancreas with rising incidence in many countries. Despite improvements in diagnostic techniques, the disease is associated with high risk of severe morbidity and mortality and there is an urgent need for new therapeutic interventions. In this study, we evaluated whether histone deacetylases (HDACs), key epigenetic regulators of gene transcription, are involved in the development of the disease. EXPERIMENTAL APPROACH: We analysed HDAC regulation during cerulein-induced acute, chronic and autoimmune pancreatitis using different transgenic mouse models...
November 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28819194/hdac3-inhibition-ameliorates-spinal-cord-injury-by-immunomodulation
#10
Tomoharu Kuboyama, Shalaka Wahane, Yong Huang, Xiang Zhou, Jamie K Wong, Andrew Koemeter-Cox, Michael Martini, Roland H Friedel, Hongyan Zou
Following spinal cord injury (SCI), the innate immune response of microglia and infiltrating macrophages clears up cellular debris and promotes tissue repair, but it also inflicts secondary injury from inflammatory responses. Immunomodulation aimed at maximizing the beneficial effects while minimizing the detrimental roles of the innate immunity may aid functional recovery after SCI. However, intracellular drivers of global reprogramming of the inflammatory gene networks in the innate immune cells are poorly understood...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28812434/-pemetrexed-sildenafil-via-autophagy-dependent-hdac-downregulation-enhances-the-immunotherapy-response-of-nsclc-cells
#11
Laurence Booth, Jane L Roberts, Andrew Poklepovic, Paul Dent
Pemetrexed is an approved therapeutic in NSCLC and ovarian cancer. Our studies focused on the ability of [pemetrexed + sildenafil] exposure to alter the immunogenicity of lung and ovarian cancer cells. Treatment of lung and ovarian cancer cells with [pemetrexed + sildenafil] in vitro rapidly reduced the expression of PD-L1, PD-L2 and ornithine decarboxylase (ODC), and increased the expression of class I MHCA. In a cell-specific fashion, some cells also released the immunogenic nuclear protein HMGB1 into the extracellular environment...
September 2, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28791019/macrophage-inducible-c-type-lectin-as-a-multifunctional-player-in-immunity
#12
REVIEW
Emmanuel C Patin, Selinda Jane Orr, Ulrich E Schaible
The macrophage-inducible C-type lectin (Mincle) is an innate immune receptor on myeloid cells sensing diverse entities including pathogens and damaged cells. Mincle was first described as a receptor for the mycobacterial cell wall glycolipid, trehalose-6,6'-dimycolate, or cord factor, and the mammalian necrotic cell-derived alarmin histone deacetylase complex unit Sin3-associated protein 130. Upon engagement by its ligands, Mincle induces secretion of innate cytokines and other immune mediators modulating inflammation and immunity...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28733560/mir-122-socs1-jak2-axis-regulates-allergic-inflammation-and-allergic-inflammation-promoted-cellular-interactions
#13
Kyeonga Noh, Misun Kim, Youngmi Kim, Hanearl Kim, Hyuna Kim, Jaehwan Byun, Yeongseo Park, Hansoo Lee, Yun Sil Lee, Jongseon Choe, Young Myeong Kim, Dooil Jeoung
The regulatory role of suppressor of cytokine signaling 1 (SOCS1) in inflammation has been reported. However, its role in allergic inflammation has not been previously reported. SOCS1 mediated in vitro and in vivo allergic inflammation. Histone deacetylase-3 (HDAC3), a mediator of allergic inflammation, interacted with SOCS1, and miR-384 inhibitor, a positive regulator of HDAC3, induced features of allergic inflammation in an SOCS1-dependent manner. miRNA array analysis showed that the expression of miR-122 was decreased by antigen-stimulation...
July 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28719070/sirtuin-1-attenuates-inflammation-and-hepatocellular-damage-in-liver-transplant-ischemia-reperfusion-from-mouse-to-human
#14
Kojiro Nakamura, Shoichi Kageyama, Bibo Ke, Takehiro Fujii, Rebecca A Sosa, Elaine F Reed, Nakul Datta, Ali Zarrinpar, Ronald W Busuttil, Jerzy W Kupiec-Weglinski
Hepatic ischemia/reperfusion injury (IRI), an inevitable antigen-independent inflammation response in cadaveric liver transplantation, correlates with poor early graft function, rejection episodes, and contributes to donor organ shortage. Sirtuin 1 (SIRT1) is a histone deacetylase that may regulate inflammatory cell activity and manage liver function in IRI, though its functional role and clinical relevance remains to be elucidated. We investigated the efficacy of SIRT1 activation in a murine liver IRI model and verified the concept of putative SIRT1-mediated hepatoprotection in clinical liver transplantation...
October 2017: Liver Transplantation
https://www.readbyqxmd.com/read/28696255/regulated-polarization-of-tumor-associated-macrophages-by-mir-145-via-colorectal-cancer-derived-extracellular-vesicles
#15
Haruka Shinohara, Yuki Kuranaga, Minami Kumazaki, Nobuhiko Sugito, Yuki Yoshikawa, Tomoaki Takai, Kohei Taniguchi, Yuko Ito, Yukihiro Akao
Macrophages are polarized into functional classically activated and alternatively activated (M2) phenotypes depending on their microenvironment, and these cells play an important role in the immune system. M2-like polarization of tumor-associated macrophages (TAMs) is activated by various secretions from cancer cells; however, the interaction between cancer cells and TAMs is not well understood. Recent studies showed that cancer cell-derived extracellular vesicles (EVs) contribute to tumor development and modulation of the tumor microenvironment...
August 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28681454/human-monocytes-downregulate-innate-response-receptors-following-exposure-to-the-microbial-metabolite-n-butyrate
#16
Felix Lasitschka, Thomas Giese, Marco Paparella, Stefan R Kurzhals, Guido Wabnitz, Katrin Jacob, Judith Gras, Konrad A Bode, Anne-Kristin Heninger, Timea Sziskzai, Yvonne Samstag, Cornelia Leszinski, Bettina Jocher, Mohammed Al-Saeedi, Stefan C Meuer, Jutta Schröder-Braunstein
INTRODUCTION: Hyporesponsiveness of human lamina propria immune cells to microbial and nutritional antigens represents one important feature of intestinal homeostasis. It is at least partially mediated by low expression of the innate response receptors CD11b, CD14, CD16 as well as the cystine-glutamate transporter xCT on these cells. Milieu-specific mechanisms leading to the down-regulation of these receptors on circulating monocytes, the precursor cells of resident macrophages, are mostly unknown...
July 6, 2017: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/28673995/inhibition-of-acute-lethal-pulmonary-inflammation-by-the-ido-ahr-pathway
#17
Soung-Min Lee, Ha Young Park, Young-Sill Suh, Eun Hye Yoon, Juyang Kim, Won Hee Jang, Won-Sik Lee, Sae-Gwang Park, Il-Whan Choi, Inhak Choi, Sun-Woo Kang, Hwayoung Yun, Takanori Teshima, Byungsuk Kwon, Su-Kil Seo
The lung is a prototypic organ that was evolved to reduce immunopathology during the immune response to potentially hazardous endogenous and exogenous antigens. In this study, we show that donor CD4(+) T cells transiently induced expression of indoleamine 2,3-dioxygenase (IDO) in lung parenchyma in an IFN-γ-dependent manner early after allogeneic hematopoietic stem cell transplantation (HSCT). Abrogation of host IDO expression by deletion of the IDO gene or the IFN-γ gene in donor T cells or by FK506 treatment resulted in acute lethal pulmonary inflammation known as idiopathic pneumonia syndrome (IPS)...
July 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28668087/inhibition-of-hdac6-activity-through-interaction-with-ranbpm-and-its-associated-ctlh-complex
#18
Louisa M Salemi, Matthew E R Maitland, Eyal R Yefet, Caroline Schild-Poulter
BACKGROUND: Histone deacetylase 6 (HDAC6) is a microtubule-associated deacetylase that promotes many cellular processes that lead to cell transformation and tumour development. We previously documented an interaction between Ran-Binding Protein M (RanBPM) and HDAC6 and found that RanBPM expression inhibits HDAC6 activity. RanBPM is part of a putative E3 ubiquitin ligase complex, termed the C-terminal to LisH (CTLH) complex. Here, we investigated the involvement of the CTLH complex on HDAC6 inhibition and assessed the outcome of this regulation on the cellular motility induced by HDAC6...
July 1, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28661460/the-novel-hdac8-inhibitor-wk2-16-attenuates-lipopolysaccharide-activated-matrix-metalloproteinase-9-expression-in-human-monocytic-cells-and-improves-hypercytokinemia-in-vivo
#19
Jing-Shiun Jan, Yung-Chen Chou, Yu-Wen Cheng, Chih-Kuang Chen, Wei-Jan Huang, George Hsiao
Dysregulated human monocytes/macrophages can synthesize and secrete matrix metalloproteinases (MMPs), which play important roles in the progression of sepsis. In this study, we investigated the effects and mechanism of a novel histone deacetylase (HDAC8) inhibitor, (E)-N-hydroxy-4-methoxy-2-(biphenyl-4-yl)cinnamide (WK2-16), on MMP-9 production and activation in stimulated human monocytic THP-1 cells. Our results demonstrated that the acetylation level of structural maintenance of chromosomes 3 (SMC3) was up-regulated by WK2-16 in THP-1 cells...
June 29, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28658622/lanosterol-modulates-tlr4-mediated-innate-immune-responses-in-macrophages
#20
Elisa Araldi, Marta Fernández-Fuertes, Alberto Canfrán-Duque, Wenwen Tang, Gary W Cline, Julio Madrigal-Matute, Jordan S Pober, Miguel A Lasunción, Dianqing Wu, Carlos Fernández-Hernando, Yajaira Suárez
Macrophages perform critical functions in both innate immunity and cholesterol metabolism. Here, we report that activation of Toll-like receptor 4 (TLR4) in macrophages causes lanosterol, the first sterol intermediate in the cholesterol biosynthetic pathway, to accumulate. This effect is due to type I interferon (IFN)-dependent histone deacetylase 1 (HDAC1) transcriptional repression of lanosterol-14α-demethylase, the gene product of Cyp51A1. Lanosterol accumulation in macrophages, because of either treatment with ketoconazole or induced conditional disruption of Cyp51A1 in mouse macrophages in vitro, decreases IFNβ-mediated signal transducer and activator of transcription (STAT)1-STAT2 activation and IFNβ-stimulated gene expression...
June 27, 2017: Cell Reports
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