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histone deacetylase T cells

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https://www.readbyqxmd.com/read/28819166/histone-protein-deacetylase-11-targeting-promotes-foxp3-treg-function
#1
Jianbing Huang, Liqing Wang, Satinder Dahiya, Ulf H Beier, Rongxiang Han, Arabinda Samanta, Joel Bergman, Eduardo M Sotomayor, Edward Seto, Alan P Kozikowski, Wayne W Hancock
Current interest in Foxp3+ T-regulatory (Treg) cells as therapeutic targets in transplantation is largely focused on their harvesting pre-transplant, expansion and infusion post-transplantation. An alternate strategy of pharmacologic modulation of Treg function using histone/protein deacetylase inhibitors (HDACi) may allow more titratable and longer-term dosing. However, the effects of broadly acting HDACi vary, such that HDAC isoform-selective targeting is likely required. We report data from mice with constitutive or conditional deletion of HDAC11 within Foxp3+ Treg cells, and their use, along with small molecule HDAC11 inhibitors, in allograft models...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28814661/hdac-inhibition-induces-hiv-1-protein-and-enables-immune-based-clearance-following-latency-reversal
#2
Guoxin Wu, Michael Swanson, Aarthi Talla, Donald Graham, Julie Strizki, Daniel Gorman, Richard Jo Barnard, Wade Blair, Ole S Søgaard, Martin Tolstrup, Lars Østergaard, Thomas A Rasmussen, Rafick-Pierre Sekaly, Nancie M Archin, David M Margolis, Daria J Hazuda, Bonnie J Howell
Promising therapeutic approaches for eradicating HIV include transcriptional activation of provirus from latently infected cells using latency-reversing agents (LRAs) and immune-mediated clearance to purge reservoirs. Accurate detection of cells capable of producing viral antigens and virions, and the measurement of clearance of infected cells, is essential to assessing therapeutic efficacy. Here, we apply enhanced methodology extending the sensitivity limits for the rapid detection of subfemtomolar HIV gag p24 capsid protein in CD4+ T cells from ART-suppressed HIV+ individuals, and we show viral protein induction following treatment with LRAs...
August 17, 2017: JCI Insight
https://www.readbyqxmd.com/read/28812434/-pemetrexed-sildenafil-via-autophagy-dependent-hdac-down-regulation-enhances-the-immunotherapy-response-of-nsclc-cells
#3
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...
August 16, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28812327/design-and-synthesis-of-terephthalic-acid-based-histone-deacetylase-inhibitors-with-dual-stage-anti-plasmodium-activity
#4
Katharina Stenzel, Ming Jang Chua, Sandra Duffy, Yevgeniya Antonova-Koch, Stephan Meister, Alexandra Hamacher, Matthias U Kassack, Elizabeth A Winzeler, Vicky M Avery, Thomas Kurz, Katherine T Andrews, Finn Kristian Hansen
In this work we aimed to develop parasite-selective HDAC inhibitors with activity against the disease-causing asexual blood stages of Plasmodium as well as causal prophylactic and/or transmission blocking properties. We report the design, synthesis and biological testing of a series of 13 terephthalic acid-based histone deacetylase inhibitors. All compounds showed low cytotoxicity against human embryonic kidney (HEK293) cells (IC50 8 - >51 µM), with 11 also having sub-micromolar in vitro activity against drug-sensitive (3D7) and multi-drug resistant (Dd2) asexual blood stage Plasmodium falciparum parasites (IC50 ~ 0...
August 15, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28809557/in-silico-and-in-vitro-interactions-between-short-chain-fatty-acids-and-human-histone-deacetylases
#5
Rou Hui Ho, James Chun Yip Chan, Hao Fan, Dorinda Yan Qin Kioh, Bee Wah Lee, Eric Chun Yong Chan
Short chain fatty acids (SCFAs) are postulated to modulate the immune development of neonates via epigenetic regulations such as histone deacetylase (HDAC) inhibition. In the context of atopic diseases, the inhibition of HDAC maintains T-cell homeostasis and induces naïve T-cell differentiation into adaptive Treg, which regulates the production of anti-inflammatory cytokines and suppression of Th2 immune responses. We investigated the structure-inhibition relationships of SCFAs with class I HDAC3 and class IIa HDAC7 using in silico docking simulation and in vitro human recombinant HDAC inhibition assay...
August 15, 2017: Biochemistry
https://www.readbyqxmd.com/read/28799436/immunotherapy-based-approaches-in-myelofibrosis
#6
Lucia Masarova, Srdan Verstovsek, Hagop Kantarjian, Naval Daver
Aberrant regulation of the immune system with up-regulation of pro-inflammatory cytokines contributes to disease pathophysiology in myelofibrosis (MF). Therapeutic options for MF associated anemia, thrombocytopenia, and bone marrow fibrosis remain limited. Areas covered: This review focuses on immune based therapies in MF, including immunomodulatory imide drugs (IMiDs), interferons, monoclonal antibodies and targeted agents (SL-401), and checkpoint inhibitors. Published literature was reviewed using available databases (PubMed, Cochrane, Scopus) and web pages (clinicaltrials...
August 11, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28782836/histone-deacetylase-3-deletion-in-mesenchymal-progenitor-cells-hinders-long-bone-development
#7
Marina Feigenson, Lomeli Carpio Shull, Earnest L Taylor, Emily T Camilleri, Scott M Reister, Andre J van Wijnen, Elizabeth W Bradley, Jennifer J Westendorf
Long bone formation is a complex process that requires precise transcriptional control of gene expression programs in mesenchymal progenitor cells. Histone deacetylases (Hdacs) coordinate chromatin structure and gene expression by enzymatically removing acetyl groups from histones and other proteins. Hdac inhibitors are used clinically to manage mood disorders, cancers and other conditions, but are teratogenic to the developing skeleton and increase fracture risk in adults. In this study, the functions of Hdac3, one of the enzymes blocked by current Hdac inhibitor therapies, in skeletal mesenchymal progenitor cells were determined...
August 7, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28769891/histone-deacetylase-2-is-a-component-of-influenza-a-virus-induced-host-antiviral-response
#8
Prashanth T Nagesh, Mazhar Hussain, Henry D Galvin, Matloob Husain
Host cells produce variety of antiviral factors that create an antiviral state and target various stages of influenza A virus (IAV) life cycle to inhibit infection. However, IAV has evolved various strategies to antagonize those antiviral factors. Recently, we reported that a member of class I host histone deacetylases (HDACs), HDAC1 possesses an anti-IAV function. Herein, we provide evidence that HDAC2, another class I member and closely related to HDAC1 in structure and function, also possesses anti-IAV properties...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28763903/-role-of-roxithromycin-on-glucocorticoid-resistance-of-human-bronchial-epithelial-cells-and-its-mechanism
#9
D D Sun, T T Xu, W F Zhou, Y R Dai
Objective: To explore the effects of roxithromycin (RXM) on glucocorticoid resistance of human bronchial epithelial cells exposed to smoke and its mechanism. Methods: Beas-2B cells as the research object were grouped into: control group, 10%cigarette smoke extract (CSE) group, roxithromycin (RXM)+ 10%CSE group. With 10%CSE intervention in the 10%CSE group, 10%CSE and RXM intervention in the RXM+ 10%CSE group, complete culture solution intervention in the control group. Interleukin-8 (IL-8) levels were measured by enzyme linked immunosorbent assay (ELISA) and IL-8 inhibition rate and dexamethasone half inhibitory concentration (IC50-Dex) were calculated; the expression of histone deacetylase 2 (HDAC2) protein was detected by immunofluorescence (IF) and Western blotting (WB)...
July 25, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28754906/kras-activation-and-over-expression-of-sirt1-bcl6-contributes-to-the-pathogenesis-of-endometriosis-and-progesterone-resistance
#10
Jung-Yoon Yoo, Tae Hoon Kim, Asgerally T Fazleabas, Wilder A Palomino, Soo Hyun Ahn, Chandrakant Tayade, David P Schammel, Steven L Young, Jae-Wook Jeong, Bruce A Lessey
Endometriosis is an inflammatory condition that is associated with progesterone resistance and cell proliferation, resulting in pain, infertility and pregnancy loss. We previously demonstrated phosphorylation of STAT3 in eutopic endometrium of infertile women with this disorder leading to over-expression of the oncogene BCL6 and stabilization of hypoxia-induced factor 1 alpha (HIF-1α). Here we report coordinated activation of KRAS and over-expression of Sirtuin 1 (SIRT1), a histone deacetylase and gene silencer, in the eutopic endometrium from women with endometriosis throughout the menstrual cycle...
July 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28736194/the-epigenetic-drug-trichostatin-a-ameliorates-experimental-autoimmune-encephalomyelitis-via-t-cell-tolerance-induction-and-impaired-influx-of-t-cells-into-the-spinal-cord
#11
Arathi Jayaraman, Advait Soni, Bellur S Prabhakar, Mark Holterman, Sundararajan Jayaraman
Multiple sclerosis is a T cell mediated chronic demyelinating disease of the central nervous system. Although currently available therapies reduce relapses, they do not facilitate tolerization of myelin antigen-specific T lymphocytes to ensure prolonged protection against multiple sclerosis. Here, we show that treatment of NOD mice with the histone deacetylase inhibitor, Trichostatin A affords robust protection against myelin peptide induced experimental autoimmune encephalomyelitis, a mouse model of multiple sclerosis...
July 20, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28733560/mir-122-socs1-jak2-axis-regulates-allergic-inflammation-and-allergic-inflammation-promoted-cellular-interactions
#12
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/28724935/histone-deacetylase-3-is-required-for-inkt-cell-development
#13
Puspa Thapa, Sinibaldo Romero Arocha, Ji Young Chung, Derek B Sant'Angelo, Virginia Smith Shapiro
NKT cells are a distinct subset that have developmental requirements that often differ from conventional T cells. Here, we show that NKT-specific deletion of Hdac3 results in a severe reduction in the number of iNKT cells, particularly of NKT1 cells. In addition, there is decreased cytokine production by Hdac3-deficient NKT2 and NKT17 cells. Hdac3-deficient iNKT cells have increased cell death that is not rescued by transgenic expression of Bcl-2 or Bcl-xL. Hdac3-deficient iNKT cells have less Cyto-ID staining and lower LC3A/B expression, indicative of reduced autophagy...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28720877/role-of-the-histone-deacetylase-inhibitor-valproic-acid-in-high-fat-diet-induced-hypertension-via-inhibition-of-hdac1-angiotensin-ii-axis
#14
J Choi, S Park, T K Kwon, S I Sohn, K M Park, J I Kim
BACKGROUND: Obesity is known as an epidemic worldwide because of consumption of westernized high-fat diets and one of the major risk factors of hypertension. Histone deacetylases (HDACs) control gene expression by regulating histone/non-histone protein deacetylation. HDAC inhibitors exert anti-cancer and anti-inflammatory effects and play a protective role in cardiovascular diseases. In the present study, we tested the effect of an FDA-approved pan-HDAC inhibitor valproic acid (VPA) on high-fat diet (HFD)-induced hypertension in mice...
July 19, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28714868/interval-dosing-with-the-hdac-inhibitor-vorinostat-effectively-reverses-hiv-latency
#15
Nancie M Archin, Jennifer L Kirchherr, Julia Am Sung, Genevieve Clutton, Katherine Sholtis, Yinyan Xu, Brigitte Allard, Erin Stuelke, Angela D Kashuba, Joann D Kuruc, Joseph Eron, Cynthia L Gay, Nilu Goonetilleke, David M Margolis
BACKGROUND: The histone deacetylase (HDAC) inhibitor vorinostat (VOR) can increase HIV RNA expression in vivo within resting CD4+ T cells of aviremic HIV+ individuals. However, while studies of VOR or other HDAC inhibitors have reported reversal of latency, none has demonstrated clearance of latent infection. We sought to identify the optimal dosing of VOR for effective serial reversal of HIV latency. METHODS: In a study of 16 HIV-infected, aviremic individuals, we measured resting CD4+ T cell-associated HIV RNA ex vivo and in vivo following a single exposure to VOR, and then in vivo after a pair of doses separated by 48 or 72 hours, and finally following a series of 10 doses given at 72-hour intervals...
August 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28697338/hdac-inhibitors-finally-open-up-chromatin-accessibility-signatures-of-ctcl
#16
Christopher J Ott, Catherine J Wu
In this issue of Cancer Cell, Qu et al. describe the chromatin accessibility profiles of cutaneous T cell lymphoma, with dynamic assessments of response and resistance to histone deacetylase inhibitor therapy. Their "personal regulome" analysis framework reveals chromatin features that may be predictive of clinical response to epigenetic therapy.
July 10, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28695331/vorinostat-and-mithramycin-a-in-combination-therapy-as-an-interesting-strategy-for-the-treatment-of-s%C3%A3-zary-t-lymphoma-a-transcriptomic-approach
#17
R Ragheb, G Venton, R Chelbi, N Bonnet, T Le Treut, V Ivanov, C Mercier, P Poulin, N Beaufils, J Gabert, P Suchon, P Rihet, B Loriod, B Kahn-Perlès, Régis T Costello
SAHA (vorinostat) is a histone deacetylase inhibitor approved by the USA Food and Drug Administration (FDA) for treating advanced refractory cutaneous T cell lymphomas. As SAHA alters the expression of many genes under control of the Sp1 transcription factor, we examined the effect of its association with the FDA-approved anticancer antibiotic Mithramycin A (MTR, plicamycin), a competitive inhibitor of Sp1 binding to DNA. Sézary syndrome (SS) cells, expanded ex vivo from peripheral blood mononuclear cells of 4 patients, were tested for their sensitivity to the drugs regarding cytotoxicity and differential responsive gene expression...
July 10, 2017: Archives of Dermatological Research
https://www.readbyqxmd.com/read/28693431/the-attenuation-of-renal-fibrosis-by-histone-deacetylase-inhibitors-is-associated-with-the-plasticity-of-foxp3-il-17-t-cells
#18
Wen-Pyng Wu, Yi-Giien Tsai, Tze-Yi Lin, Ming-Ju Wu, Ching-Yuang Lin
BACKGROUND: The histone deacetylase (HDAC) inhibitor, which has potential effects on epigenetic modifications, had been reported to attenuate renal fibrosis. CD4(+) forkhead box P3 (FOXP3)(+) T regulatory (Treg) cells may be converted to inflammation-associated T helper 17 cells (Th17) with tissue fibrosis properties. The association between FOXP3(+)IL-17(+) T cells and the attenuation of renal fibrosis by the HDAC inhibitor is not clear. METHODS: This study evaluated the roles of the HDAC inhibitor, Treg cells and their differentiation into Th17 cells, which aggravate chronic inflammation and renal fibrosis in a unilateral ureteral obstruction (UUO) mouse model...
July 10, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28689087/the-histone-deacetylase-inhibitor-saha-simultaneously-reactivates-hiv-1-from-latency-and-up-regulates-nkg2d-ligands-sensitizing-for-natural-killer-cell-cytotoxicity
#19
Maria Giovanna Desimio, Erica Giuliani, Margherita Doria
In pilot HIV-1 eradication studies, patients' immune responses were ineffective at killing viral reservoirs reactivated through latency reversing agents (LRAs) like suberoylanilide hydroxamic acid (SAHA). We hypothesized that T cells harboring reactivated HIV-1 express MIC and ULBP ligands for the activating NKG2D receptor of natural killer (NK) cells. Here, we demonstrated that MICA/B and ULBP2 are induced by SAHA on primary T cells harboring reactivated virus. Using latently HIV-1-infected J-Lat 6.3/8.4/9...
July 6, 2017: Virology
https://www.readbyqxmd.com/read/28673995/inhibition-of-acute-lethal-pulmonary-inflammation-by-the-ido-ahr-pathway
#20
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
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