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histone deacetylase inflammation

Jiangying Kuang, Lei Chen, Qin Tang, Jinhang Zhang, Yanping Li, Jinhan He
Sirt6 is one of the sirtuin family members, a kind of NAD+-dependent histone deacetylase and ADP-ribose transferase enzyme. It has an important role in physiological and pathological processes, regulating aging, cancer, obesity, insulin resistance, inflammation, and energy metabolism. Recent studies have suggested that reduced Sirt6 action is related to obesity and diabetes. Aging and overnutrition, two major risk factors for obesity and diabetes, lead to decreased Sirt6 level and function, which results in abnormal glucose and lipid metabolism...
2018: Frontiers in Physiology
Di Yang, ChenXi Xiao, Fen Long, ZhengHua Su, WanWan Jia, Ming Qin, MengWei Huang, WeiJun Wu, Rinkiko Suguro, XinHua Liu, YiZhun Zhu
Aims: Angiotensin II (Ang II) causes vascular inflammation, leading to vascular endothelial cell dysfunction, and is associated with the development of cardiovascular diseases. Therefore, interventions in inflammation may contribute to the reduction of cardiovascular diseases. Here, we aim to demonstrate that HDAC4, one of class IIa family histone deacetylases (HDACs) members, promotes autophagy-dependent vascular inflammation. Methods and results: By loss-of-function approaches, our study provides the first evidence that HDAC4 mediates Ang II-induced vascular inflammation in vitro and in vivo...
February 24, 2018: Cardiovascular Research
Michelle L Ratay, Stephen C Balmert, Ethan J Bassin, Steven R Little
Dry eye disease (DED), also known as keratoconjunctivitis sicca, is an ocular surface disease characterized by T-cell-mediated inflammation. Current therapeutics, such as immunosuppressive agents, act to suppress the clinical signs and inflammation. However, long-term usage of these treatments can cause severe side effects. In this study, we present an alternative therapeutic approach that utilizes a histone deacetylase inhibitor (HDACi) to regulate transcription of a variety of immunomodulatory genes. Specifically, HDACi have emerged as a potential anti-inflammatory agent, which can modulate the functions of a subset of suppressive T lymphocytes known as regulatory T cells (Tregs), enhancing FoxP3 acetylation and subsequently guarding the transcription factor from proteasomal degradation...
March 8, 2018: Acta Biomaterialia
Pan Pan, Kiyoko Oshima, Yi-Wen Huang, Kimberle A Agle, William R Drobyski, Xiao Chen, Jianying Zhang, Martha M Yearsley, Jianhua Yu, Li-Shu Wang
Free fatty acid receptor 2 (FFAR2, also named GPR43), is activated by short-chain fatty acids (SCFAs), such as butyrate, that are produced when gut bacteria ferment dietary fiber. FFAR2 has been suggested to regulate colonic inflammation, which is a major risk factor for the development of colon cancer and is also linked to epigenetic dysregulation in colon carcinogenesis. The current study assessed whether FFAR2, acting as an epigenetic regulator, protects against colon carcinogenesis. To mimic the mild inflammation that promotes human colon cancer, we treated mice with dextran sodium sulfate (DSS) overnight, which avoids excessive inflammation but induces mild inflammation that promotes colon carcinogenesis in the ApcMin/+ and the azoxymethane (AOM)-treated mice...
March 9, 2018: International Journal of Cancer. Journal International du Cancer
Clare A Stokes, Alison M Condliffe
Defining features of chronic airway diseases include abnormal and persistent inflammatory processes, impaired airway epithelial integrity and function, and increased susceptibility to recurrent respiratory infections. Phosphoinositide 3-kinases (PI3K) are lipid kinases, which contribute to multiple physiological and pathological processes within the airway, with abnormal PI3K signalling contributing to the pathogenesis of several respiratory diseases. Consequently, the potential benefit of targeting PI3K isoforms has received considerable attention, being viewed as a viable therapeutic option in inflammatory and infectious lung disorders...
March 9, 2018: Biochemical Society Transactions
Christina Li-Ping Thio, Po-Yu Chi, Alan Chuan-Ying Lai, Ya-Jen Chang
BACKGROUND: Allergic asthma is characterized airway hyperreactivity (AHR) and inflammation driven by aberrant TH 2 response. Type 2 innate lymphoid cells (ILC2s) are a critical source of TH 2 cytokines IL-5 and IL-13 which promote acute asthma exacerbation. Short chain fatty acids (SCFAs) have been shown to attenuate T cell-mediated allergic airway inflammation. Their role in the regulation of ILC2-driven AHR and lung inflammation, however, remains unknown. OBJECTIVE: We investigated the immunomodulatory role of SCFAs in the regulation of ILC2-induced AHR and airway inflammation and delineated the mechanism involved...
March 6, 2018: Journal of Allergy and Clinical Immunology
Sandrine Herbelet, Elly De Vlieghere, Amanda Gonçalves, Boel De Paepe, Karsten Schmidt, Eline Nys, Laurens Weynants, Joachim Weis, Gert Van Peer, Jo Vandesompele, Jens Schmidt, Olivier De Wever, Jan L De Bleecker
Aims: Regeneration in skeletal muscle relies on regulated myoblast migration and differentiation, in which the transcription factor nuclear factor of activated T-cells 5 (NFAT5) participates. Impaired muscle regeneration and chronic inflammation are prevalent in myositis. Little is known about the impact of inflammation on NFAT5 localization and expression in this group of diseases. The goal of this study was to investigate NFAT5 physiology in unaffected myoblasts exposed to cytokine or hyperosmolar stress and in myositis...
2018: Frontiers in Physiology
Xue Zhang, Wuping Bao, Xia Fei, Yingying Zhang, Guoqing Zhang, Xin Zhou, Min Zhang
Airway remodeling is a vital component of chronic obstructive pulmonary disease (COPD). Despite the broad anti-inflammation effects of glucocorticoids, they exhibit relatively little therapeutic benefit in COPD, indicating the accelerating demands of new agents for COPD. We aim to explore the effect of progesterone on airway remodeling in a murine modeling of exposing to ozone and to further examine the potential effect of progesterone on glucocorticoid insensitivity. C57/BL6 mice were exposed to ozone for 12 times over 6 weeks, and were administered with progesterone alone or combined with budesonide (BUD) after each exposure until the 10th week...
March 1, 2018: Molecular Immunology
Fangyuan Cao, Martijn R H Zwinderman, Frank J Dekker
Histone deacetylases (HDACs) are epigenetic drug targets that have gained major scientific attention. Inhibition of these important regulatory enzymes is used to treat cancer, and has the potential to treat a host of other diseases. However, currently marketed HDAC inhibitors lack selectivity for the various HDAC isoenzymes. Several studies have shown that HDAC3, in particular, plays an important role in inflammation and degenerative neurological diseases, but the development of selective HDAC3 inhibitors has been challenging...
March 2, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Eva Pigna, Alessandra Renzini, Emanuela Greco, Elena Simonazzi, Stefania Fulle, Rosa Mancinelli, Viviana Moresi, Sergio Adamo
BACKGROUND: Denervation triggers numerous molecular responses in skeletal muscle, including the activation of catabolic pathways and oxidative stress, leading to progressive muscle atrophy. Histone deacetylase 4 (HDAC4) mediates skeletal muscle response to denervation, suggesting the use of HDAC inhibitors as a therapeutic approach to neurogenic muscle atrophy. However, the effects of HDAC4 inhibition in skeletal muscle in response to long-term denervation have not been described yet...
February 24, 2018: Skeletal Muscle
Jie Xia, Huabin Hu, Wenjie Xue, Xiang Simon Wang, Song Wu
Histone deacetylase 3 (HDAC3) is a potential target for the treatment of human diseases such as cancers, diabetes, chronic inflammation and neurodegenerative diseases. Previously, we proposed a virtual screening (VS) pipeline named "Hypo1_FRED_SAHA-3" for the discovery of HDAC3 inhibitors (HDAC3Is) and had thoroughly validated it by theoretical calculations. In this study, we attempted to explore its practical utility in a large-scale VS campaign. To this end, we used the VS pipeline to hierarchically screen the Specs chemical library...
December 2018: Journal of Enzyme Inhibition and Medicinal Chemistry
Jianjun Wu, Xin Li, Yang Qin, Juan Cheng, Gaimei Hao, Ruifeng Jin, Chenjun Zhu
The aim of the present study was to investigate the effect of a Traditional Chinese Herbal Medicine (TCHM), named Jinwei Tang on histone deacetylase 2 (HDAC2) and its role in the regulation of corticosteroid resistance in a rat model of chronic obstructive pulmonary disease (COPD). Male Wistar rats were divided into five groups (each n=10): COPD group, established by the intratracheal instillation of lipopolysaccharide and passive smoke exposure, and control, budesonide, theophylline + budesonide and Jinwei Tang + budesonide groups...
March 2018: Experimental and Therapeutic Medicine
Athira Kv, Rajaram Mohanrao Madhana, Indu Chandran Js, Mangala Lahkar, Swapnil Sinha, V G M Naidu
Major depressive disorder (MDD) is a multifactorial neuropsychiatric disorder. Chronic administration of corticosterone (CORT) to rodents is used to mimic the stress associated dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, a well-established feature found in depressive patients. Recently, preclinical studies have demonstrated the antidepressant potential of histone deacetylase (HDAC) inhibitors. So, we examined the antidepressant potential of vorinostat (VOR), a HDAC inhibitor against CORT injections in male mice...
February 13, 2018: Behavioural Brain Research
Carlotta Granchi, Filippo Minutolo
SIRT1 is a nicotinamide adenosine dinucleotide (NAD+)-dependent deacetylase, which removes acetyl groups from many target proteins, such as histone proteins, transcription factors and cofactors. SIRT1-catalyzed deacetylation of these factors modulates the activity of downstream proteins, thus influencing many biological processes. SIRT1 is involved in the regulation of metabolism, inflammation, and tumor growth. The activity of this enzyme is related to the beneficial health effects of calorie restriction, such as lifespan extension and, in particular, the activation of SIRT1 has a positive impact on the cardiovascular system...
February 13, 2018: Current Medicinal Chemistry
Beatriz Fernandez-Fernandez, M Concepcion Izquierdo, Lara Valiño-Rivas, Dimitra Nastou, Ana B Sanz, Alberto Ortiz, Maria D Sanchez-Niño
Background: Kidney tubular cells are the main sources of Klotho, a protein with phosphaturic action. Genetic Klotho deficiency causes premature cardiovascular aging in mice. Human chronic kidney disease (CKD) is characterized by acquired Klotho deficiency. Despite the lack of uremic toxin accumulation, Category G1 CKD [(normal glomerular filtration rate (GFR)] is already associated with decreased Klotho and with premature cardiovascular aging. Methods: We have explored whether albuminuria, a criterion to diagnose CKD when GFR is normal, may directly decrease Klotho expression in human CKD, preclinical models and cultured tubular cells...
February 7, 2018: Nephrology, Dialysis, Transplantation
Jingjing Wang, Lilei Zhao, Zhengkai Wei, Xu Zhang, Yanan Wang, Fan Li, Yunhe Fu, Bin Liu
Histone deacetylase 6 (HDAC6) is the sole member of the HDAC family, that is predominantly located in the cytoplasm and has substrate specificity for nonhistone proteins, such as α-Tubulin. Although an increasing number of studies have shown that HDAC6 is involved in inflammatory diseases, but little is known about the participation of HDAC6 in the transcriptional regulation of inflammatory cytokines. Here, we examined the effects of Tubastatin (Tub), a highly selective HDAC6 inhibitor, on lipopolysaccharide (LPS)-stimulated primary bovine mammary epithelial cells (bMECs)...
January 27, 2018: International Immunopharmacology
Serena Di Vincenzo, Irene H Heijink, Jacobien A Noordhoek, Chiara Cipollina, Liboria Siena, Andreina Bruno, Maria Ferraro, Dirkje S Postma, Mark Gjomarkaj, Elisabetta Pace
Inflammation and ageing are intertwined in chronic obstructive pulmonary disease (COPD). The histone deacetylase SIRT1 and the related activation of FoxO3 protect from ageing and regulate inflammation. The role of SIRT1/FoxO3 in COPD is largely unknown. This study evaluated whether cigarette smoke, by modulating the SIRT1/FoxO3 axis, affects airway epithelial pro-inflammatory responses. Human bronchial epithelial cells (16HBE) and primary bronchial epithelial cells (PBECs) from COPD patients and controls were treated with/without cigarette smoke extract (CSE), Sirtinol or FoxO3 siRNA...
February 7, 2018: Journal of Cellular and Molecular Medicine
Zhongchi Li, Kang Xu, Nannan Zhang, Gabriel Amador, Yanying Wang, Sen Zhao, Liyuan Li, Ying Qiu, Zhao Wang
Sirtuin 6 (SIRT6) is a NAD+-dependent deacetylase associated with numerous aspects of health and physiology. Overexpression of SIRT6 has emerged as a protector in cardiac tissues against pathologic cardiac hypertrophy. However, the mechanism of this protective effect is not fully understood. Here, both in vivo and in vitro results demonstrated that SIRT6 overexpression can attenuate cisplatin-induced kidney injury in terms of renal dysfunction, inflammation and apoptosis. In addition, SIRT6 knockout aggravated kidney injury caused by cisplatin...
January 16, 2018: Kidney International
Marika Milan, Valentina Pace, Fabio Maiullari, Maila Chirivì, Denisa Baci, Silvia Maiullari, Luca Madaro, Sonia Maccari, Tonino Stati, Giuseppe Marano, Giacomo Frati, Pier Lorenzo Puri, Elena De Falco, Claudia Bearzi, Roberto Rizzi
Cardiovascular diseases (CVDs) are a major burden on the healthcare system: indeed, over two million new cases are diagnosed every year worldwide. Unfortunately, important drawbacks for the treatment of these patients derive from our current inability to stop the structural alterations that lead to heart failure, the common endpoint of many CVDs. In this scenario, a better understanding of the role of epigenetics - hereditable changes of chromatin that do not alter the DNA sequence itself - is warranted. To date, hyperacetylation of histones has been reported in hypertension and myocardial infarction, but the use of inhibitors for treating CVDs remains limited...
January 25, 2018: Cell Death & Disease
Silvia Perego, Veronica Sansoni, Giuseppe Banfi, Giovanni Lombardi
Butyrate, an essential factor for colonocytes and regulator in the development of colon cancer, is partially absorbed by the gut. It influences the proliferation and differentiation of several cell types including osteoblasts. We evaluated the effects of different doses of butyrate on differentiation and functionality of osteosarcoma cells in vitro and the expression of a pro-inflammatory phenotype in a normal or inflammatory environment. SaOS-2 osteosarcoma cells were induced to differentiate and contemporarily treated for 24 h, 48 h, or 7 days with sodium butyrate 10-4, 5 × 10-4, or 10-3 M in the presence or absence of tumor necrosis factor alpha (TNFα) 1 ng/mL, a pro-inflammatory stimulus...
January 2018: International Journal of Immunopathology and Pharmacology
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