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Verstak Brett B *Centre for Innate Immunity and Infectious Diseases, MIMR-PHI Institute of Medical Research, Monash University, Melbourne, Victoria, - - 2014
TLRs act as sentinels in professional immune cells to detect and initiate the innate immune response to pathogen challenge. TLR4 is a widely expressed TLR, responsible for initiating potent immune responses to LPS. TRAM acts to bridge TLR4 with TRIF, orchestrating the inflammatory response to pathogen challenge. We have identified ...
Ma Junxun - - 2012
This study examined the effect of intensive insulin therapy on immune function and inflammatory factors at the early phase after severe trauma. At day 1, 3, 5, 7 after admission, subsets of CD4(+) helper T lymphocytes (Th1/Th2) and human leukocyte antigen (HLA)-DR expression on CD14(+) monocytes were flow cytometrically measured. ...
Hsu Andy - - 2012
Dexamethasone has been a mainstay of anti-myeloma therapy for 20 years. However, it is intensely immunosuppressive and may limit the efficacy of the immune system to control myeloma, and limit the exciting opportunities to use immune stimulating drug therapies such as Lenalidomide to maximize the fight against this disease.
Wood M - - 2012
We describe the case of a newly diagnosed HIV-1-positive man who was noted to have asymptomatic HIV-related idiopathic (immune) thrombocytopaenic purpura. On commencing antiretroviral therapy we believe he experienced an uncommon immune reconstitution phenomenon resulting in the rapid worsening of his thrombocytopenia, requiring steroid therapy which stabilized his platelet levels.
Gillespie Justin J University of Leeds and NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds, - - 2012
To characterize the role of histone deacetylase (HDAC) activity in rheumatoid arthritis (RA) and to evaluate the effects of MI192, a novel HDAC-3-selective inhibitor, compared with the established nonselective HDAC inhibitor trichostatin A (TSA), on proinflammatory cytokine production. Activity of HDAC and histone acetyltransferase was measured in peripheral blood mononuclear ...
Bangert A - - 2012
Glioblastoma is the most common primary brain tumor with a very poor prognosis, calling for novel treatment strategies. Here, we provide first evidence that histone deacetylase inhibitors (HDACI) prime glioblastoma cells for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) -induced apoptosis at least in part by c-myc-mediated downregulation of cellular FLICE-inhibitory ...
Akimova Tatiana T Division of Transplant Immunology, Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104-4318, - - 2012
Clinical and experimental studies show that inhibition of histone/protein deacetylases (HDAC) can have important anti-neoplastic effects through cytotoxic and proapoptotic mechanisms. There are also increasing data from nononcologic settings that HDAC inhibitors (HDACi) can exhibit useful anti-inflammatory effects in vitro and in vivo, unrelated to cytotoxicity or apoptosis. These effects ...
Kuo Chang-Hung - - 2012
Prostaglandin I(2) (PGI(2)) analog is regarded as a potential candidate for treating asthma. Human myeloid dendritic cells (mDCs) play a critical role in the pathogenesis of asthma. However, the effects of PGI(2) analog on human mDCs are unknown. In the present study, circulating mDCs were isolated from six healthy subjects. ...
Francisco Roser - - 2011
Neuroblastoma (NB) is the most common solid extracranial tumor in children. Here we showed that trichostatin A, a histone deacetylase inhibitor (HDACi), decreases cell viability in three NB cell lines of different phenotypes. The treatment leads to G2/M-phase arrest, apoptosis and autophagy. Autophagy induction accompanies apoptosis in the most proliferative, ...
Shin Hyunsoo - - 2012
Epigenetic mechanisms of histone acetylation/deacetylation play an important role in the regulation of gene expression associated with the cell cycle and apoptosis. Recently, sodium butyrate, a histone deacetylase (HDAC) inhibitor, has been shown to exhibit anticancer effects via differentiation and apoptosis of cancer cells. Sodium butyrate may be a potential ...
Cipro Šimon - - 2012
Valproic acid (VPA), a histone deacetylase inhibitor (HDACi), has been shown to be an effective tool in cancer treatment. Although its ability to induce apoptosis has been described in many cancer types, the data come from experiments performed in normoxic (21% O2) conditions only. Therefore, we questioned whether VPA would ...
Jeong Jin Boo - - 2011
Although inflammation acts as host defense mechanism against infection or injury and is primarily a self limiting process, inadequate resolution of inflammatory responses leads to various chronic disorders. This work aimed to elucidate the anti-inflammatory effects of 2-methoxy-4-vinylphenol (2M4VP) isolated from pine needles in LPS-stimulated RAW264.7 cells. Some key pro-inflammatory ...
Mullican Shannon E SE Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104, - - 2011
Macrophages, a key cellular component of inflammation, become functionally polarized in a signal- and context-specific manner. Th2 cytokines such as interleukin 4 (IL-4) polarize macrophages to a state of alternative activation that limits inflammation and promotes wound healing. Alternative activation is mediated by a transcriptional program that is influenced by ...
Gillum Matthew P MP Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut, - - 2011
Macrophage recruitment to adipose tissue is a reproducible feature of obesity. However, the events that result in chemokine production and macrophage recruitment to adipose tissue during states of energetic excess are not clear. Sirtuin 1 (SirT1) is an essential nutrient-sensing histone deacetylase, which is increased by caloric restriction and reduced ...
Perego Paola - - 2011
Epigenetic mechanisms may contribute to drug resistance by interfering with tumor growth regulatory pathways and pro-apoptotic programs. Since gene expression is regulated by acetylation status of histones, a large variety of histone deacetylase (HDAC) inhibitors have been studied as antitumor agents. On the basis of their pro-apoptotic activity, HDAC inhibitors ...
Lee Sook-Ja - - 2011
Ku70, a DNA repair protein, was recently identified as a critical anti-apoptotic protein that inhibits Bax translocation to mitochondria. The dissociation of Bax from Ku70 is essential for the apoptotic activity of Bax. Here, we show that maspin, a tumor suppressor protein frequently lost in cancer, regulates this process. Maspin ...
Leggatt Graham R - - 2011
Acetylation of lysine residues acts to modify the function of a wide range of proteins. In histones, it affects chromatin structure, which can impact gene transcription, whereas acetylation of transcription factors and heat-shock proteins affect their activity. Deacetylase inhibitors block the dynamic turnover of acetylation resulting in hyperacetylation of target ...
Wu Chenming - - 2011
Recent studies suggest that change of macrophage phenotype (M1/M2) is associated with autoimmune diseases. Sodium valproate (VPA) is a class I histone deacetylase (HDAC) inhibitor, which has immunomodulatory function in graft-versus-host disease. However, its impact on macrophage polarization has not been defined. We evaluated the effects of VPA on both ...
Pandey Mitali M Department of Urology, Case Western Reserve University, Cleveland, Ohio 44106, - - 2012
Apigenin (4',5,7,-trihydroxyflavone), an anticancer agent, selectively toxic to cancer cells induces cell cycle arrest and apoptosis through mechanisms that have not been fully elucidated. Our studies indicate that apigenin-mediated growth inhibitory responses are due to inhibition of class I histone deacetylases (HDACs) in prostate cancer cells. Treatment of PC-3 and ...
Pérez-Perarnau Alba - - 2011
Histone deacetylases (HDACs) play a key role in the regulation of acetylation status not only of histones but also of many other non-histone proteins involved in cell cycle regulation, differentiation or apoptosis. Therefore, histone deacetylase inhibitors (HDACi) have emerged as promising anticancer agents. Herein, we report the characterization of apoptosis ...
Huang Hai - - 2011
Sterile inflammatory insults are known to activate innate immunity and propagate organ damage through the recognition of extracellular damage-associated molecular pattern (DAMP) molecules. Although DAMPs such as endogenous DNA and nuclear high-mobility group box 1 have been shown to be critical in sterile inflammation, the role of nuclear histone proteins ...
Takeuch Osamu - - 2011
Epigenetic control of gene expression is critical for cellular differentiation and development. Macrophage development, polarization and activation are also controlled by DNA and histone modifications. This Viewpoint summarizes the recent findings on the role of histone modifications regulating macrophage polarization toward M1 and M2 subtypes.
Andersen Joshua L - - 2011
Cell-fate decisions are tightly linked to cellular energy status. In this issue, Yi et al. (2011) introduce a mechanism by which Bcl-xL lowers the threshold for apoptosis by suppressing acetyl-CoA production, which, in turn, suppresses the N-alpha-acetylation important for activation of the proapoptotic protease caspase-2.
Shim Sehwan - - 2011
Ginger extracts have been reported to have anti-inflammatory, anti-oxidant, and anti-cancer effects. [6]-shogaol is one of the most bioactive components of ginger rhizomes. This study assessed the [6]-shogaol's ability to protect cultured primary rat astrocytes against lipopolysaccharide (LPS)-induced inflammation. [6]-shogaol was shown to suppress the release of pro-inflammatory cytokines and ...
Xu Jun - - 2011
We previously reported that extracellular histones are major mediators of death in sepsis. Infusion of extracellular histones leads to increased cytokine levels. Histones activate TLR2 and TLR4 in a process that is enhanced by binding to DNA. Activation of TLR4 is responsible for the histone-dependent increase in cytokine levels. To ...
Zhou Jianbiao - - 2011
Recent studies have shown that 3-Deazaneplanocin A (DZNep), a histone methyltransferase inhibitor, disrupts polycomb-repressive complex 2 (PRC2), and preferentially induces apoptosis in cancer cells, including acute myeloid leukemia (AML). However, the underlying molecular mechanisms are not well understood. The present study demonstrates that DZNep induces robust apoptosis in AML cell ...
Seong Ah-Reum - - 2011
Histone acetyltransferase (HAT) inhibitors (HATi) isolated from dietary compounds have been shown to suppress inflammatory signaling, which contributes to rheumatoid arthritis. Here, we identified a novel HATi in Punica granatum L. known as delphinidin (DP). DP did not affect the activity of other epigenetic enzymes (histone deacetylase, histone methyltransferase, or ...
Xargay-Torrent Sílvia - - 2011
Mantle cell lymphoma (MCL) is an aggressive B-cell neoplasm with generally poor prognosis, for which current therapies have shown limited efficacy. Vorinostat is a histone deacetylase inhibitor (HDACi) that has been approved for the treatment of cutaneous T-cell lymphoma. Our purpose was to describe the molecular mechanism whereby vorinostat induces ...
Shakespear Melanie R - - 2011
Histone deacetylases (HDACs) remove an acetyl group from lysine residues of target proteins to regulate cellular processes. Small-molecule inhibitors of HDACs cause cellular growth arrest, differentiation and/or apoptosis, and some are used clinically as anticancer drugs. In animal models, HDAC inhibitors are therapeutic for several inflammatory diseases, but exacerbate atherosclerosis ...
Bangert Annette - - 2011
Glioblastoma is the most common primary brain tumor with a dismal prognosis, highlighting the need for novel treatment strategies. Here, we provide the first evidence that the histone deacetylase inhibitor, MS275, sensitizes glioblastoma cells for chemotherapy-induced apoptosis. Pretreatment of glioblastoma cells with MS275 causes acetylation of histone H3 protein and ...
Mukaro Violet R S - - 2011
Apoptosis of bronchial epithelial cells and the phagocytic clearance of these cells by alveolar macrophages (a process termed efferocytosis) are integral processes leading to repair of airway epithelial injury. Efferocytosis allows for the removal of apoptotic material with minimal inflammation and prevents the development of secondary necrosis and ongoing inflammation. ...
Häcker S - - 2011
Despite aggressive therapies, the prognosis of children with high-risk medulloblastoma is still poor, thus underscoring the need to develop novel treatment strategies. Here, we report that histone deacetylase inhibitors (HDACI), that is, MS-275, valproic acid or SAHA, provide a novel strategy for sensitization of medulloblastoma to DNA-damaging drugs such as ...
Ogawa H - - 2011
Nuclear factor (NF)-κB is a transcription factor that regulates cytokine and chemokine production in various inflammatory diseases, including bronchial asthma. IκB kinase (IKK) β is important for NF-κB activation in inflammatory conditions, and is possibly related to airway remodelling. Thus, inhibition of the IKKβ-NF-κB pathway may be an ideal strategy ...
Brodská Barbora - - 2011
Reactive oxygen species play an important role in the process of apoptosis in many cell types. In this paper, we analyzed the role of ROS in DNA-damaging agents (actinomycin D or decitabine), which induced apoptosis of leukemia cell line CML-T1 and normal peripheral blood lymphocytes (PBL). The possibility of synergism ...
Xiong Ji - - 2011
Multiglycosides of Tripterygium wilfordii Hook f (GTW), a Chinese herb-derived medicine used as a remedy for rheumatoid arthritis, are considered to be a reversible anti-fertility drug affecting the mammalian spermatids. However, the mechanism behind this effect is still unknown. To study the possible mechanism behind the impact of GTW on ...
Luciani Alessandro A European Institute for Research in Cystic Fibrosis, San Raffaele Scientific Institute, Milan, - - 2011
The accumulation of misfolded and/or ubiquitinated protein aggregates with a perturbation of autophagy has been described in several human pathologies. A sequestration of misfolded cystic: fibrosis transmembrane conductance regulator (CFTR) and cross-linked PPARγ has been observed in airway epithelia of cystic fibrosis (CF) patients. CF airways are also characterized by ...
Raymond Marianne - - 2010
The interplay between innate and adaptive immune responses is essential for the establishment of allergic diseases. CD47 and its receptor, signal regulatory protein α (SIRP-α), govern innate cell trafficking. We previously reported that administration of CD47(+/+) but not CD47(-/-) SIRP-α(+) BM-derived DC (BMDC) induced airway inflammation and Th2 responses in ...
Lee Chen-Chen - - 2010
Shikonin exhibits a wide range of anti-inflammatory actions. Here, we assessed its effects on maturation of murine bone marrow-derived dendritic cells (BM-DCs) and on allergic reactions in a murine model of asthma. Cultured murine BM-DCs were used to investigate the effects of shikonin on expression of cell surface markers and ...
Yum Hye Young - - 2011
Basic fibroblast growth factor (bFGF) is a cytokine that is mitogenic for fibroblasts and smooth muscle and may play a role in airway remodeling in asthma. We have used a mouse model of chronic ovalbumin (OVA) allergen-induced airway remodeling to determine whether bFGF and fibroblast growth factor receptor-1 are expressed ...
Kawabata Yohei - - 2011
Tranilast (TL) has been clinically used for the treatment of airway inflammatory diseases, although the clinical use of TL is limited because of its poor solubility and systemic side effects. To overcome these drawbacks, a novel respirable powder of TL (CSD/TL-RP) for inhalation therapy was developed using nanocrystal solid dispersion ...
Strickland Deborah H - - 2010
Airway epithelial cells act through multiple mechanisms to function as an important component of the pulmonary defence strategy that is crucial to the maintenance of immune homeostasis. Dendritic cells are uniquely potent inducers of immune responses and it is increasingly clear that epithelium has the capacity to modulate the functional ...
Morin Caroline - - 2011
The effects of a newly synthesized docosahexaenoic acid (DHA) derivative, CRBM-0244, on lung inflammation and airway hyperresponsiveness were determined in an in vitro model of TNF-α-stimulated human bronchi and in an in vivo model of allergic asthma. Mechanical tension measurements revealed that CRBM-0244 prevented bronchial hyperresponsiveness in TNF-α-pretreated human bronchi. ...
Page Kristen - - 2011
Cockroach exposure is a major risk factor for the development of asthma; however, the early immune events induced by cockroach leading to the Th2 response are not fully understood. Exposure of naïve mice to German cockroach (GC) feces (frass) was sufficient to induce dendritic cell (DC) recruiting and activating chemokines ...
Duan Wei - - 2010
Airway tolerance is critical for protecting the lung from inflammatory disease driven by allergens. However, factors that disrupt tolerance processes and then lead to susceptibility to developing allergic asthma remain elusive. To investigate whether recognition of bacterial microbial-associated molecular patterns in the lung may result in susceptibility to developing allergic ...
Jin S-L Catherine - - 2010
Cyclic AMP (cAMP) signaling modulates functions of inflammatory cells involved in the pathogenesis of asthma, and type 4 cAMP-specific phosphodiesterases (PDE4s) are essential components of this pathway. Induction of the PDE4 isoform PDE4B is necessary for Toll-like receptor signaling in monocytes and macrophages and is associated with T cell receptor/CD3 ...
Ribeiro Carla M P - - 2010
Chronic airway infection and inflammation are hallmarks of cystic fibrosis (CF) pulmonary disease. The altered airway environment resulting from infection and inflammation can affect the innate defense of the airway epithelia. Luminal bacterial and inflammatory stimuli trigger an adaptation in human airway epithelia, characterized by a hyperinflammatory response to inflammatory ...
Ahmad Tanveer - - 2011
Asthma is a chronic airway disease characterized by increased airway hyperresponsiveness, airway inflammation, and airway remodeling including collagen deposition in subepithelial regions. We have shown earlier that mepacrine has anti-inflammatory activity and decreased the features of airway remodeling in a subacute model of asthma, when administered during the inflammatory phase. ...
Kearley Jennifer - - 2011
IL-9 is a pleiotropic cytokine that has multiple effects on structural as well as numerous hematopoietic cells, which are central to the pathogenesis of asthma. The contribution of IL-9 to asthma pathogenesis has thus far been unclear, due to conflicting reports in the literature. These earlier studies focused on the ...
Rada B - - 2011
Despite the long-appreciated in vivo role of the redox-active virulence factor pyocyanin in Pseudomonas airway infections and the importance of airway epithelial cells in combating bacterial pathogens, little is known about pyocyanin's effect on airway epithelial cells. We find that exposure of bronchiolar epithelial cells to pyocyanin results in MUC2/MUC5AC ...
Marsolais David - - 2011
Sphingosine-1-phosphate and its receptors have emerged as important modulators of the immune response. The sphingosine-1-phosphate prodrug 2-amino-2-(2-[4-octylphenyl]ethyl)-1,3-propanediol (FTY720) can alleviate experimental allergic airway inflammation. Nevertheless, the role of individual sphingosine-1-phosphate receptors in the regulation of allergic airway inflammation remains undefined. Using a newly characterized potent and selective sphingosine-1-phosphate receptor 1 ...
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