Ordered transcriptional factor recruitment and epigenetic regulation of tnf-α in necrotizing acute pancreatitis

Sandoval, Juan; Pereda, Javier; Rodrı́guez, José Luis; Escobar, Javier; Hidalgo, Juan; Joosten, Leo A. B.; Franco, Luís; Sastre, Juan; López-Rodas, Gerardo

doi:10.1007/s00018-010-0272-3

Cited by 24 publications

(26 citation statements)

References 53 publications

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“…In agreement with the histone H3 acetylation, Ad-shS1/FliC DCs also exhibited ∼6-fold increase in recruitment to the TNF-α promoter of the transcription factor sp1 ( Fig. 3B ), which was demonstrated to be important in LPS-stimulated TNF-α expression in several previous studies [28], [29]. We also found that histone H3 acetylation and sp1 recruitment to the TNF-α promoter in the Ad-shS1-transduced BMDCs were lower than those in the Ad-shS1/FliC-transduced BMDCs, but apparently higher than those in the LPS-stimulated BMDCs ( Fig.…”

Section: Resultssupporting

confidence: 88%

A Super TLR Agonist to Improve Efficacy of Dendritic Cell Vaccine in Induction of Anti-HCV Immunity

et al. 2012

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Persistent infections caused by pathogens such as hepatitis C virus are major human diseases with limited or suboptimal prophylactic and therapeutic options. Given the critical role of dendritic cell (DC) in inducing immune responses, DC vaccination is an attractive means to prevent and control the occurrence and persistence of the infections. However, DCs are built-in with inherent negative regulation mechanisms which attenuate their immune stimulatory activity and lead to their ineffectiveness in clinical application. In this study, we developed a super DC stimulant that consists of a modified, secretory Toll-like Receptor (TLR)-5 ligand and an inhibitor of the negative regulator, suppressor of cytokine sinaling-1 (SOCS1). We found that expressing the super stimulant in DCs is drastically more potent and persistent than using the commonly used DC stimuli to enhance the level and duration of inflammatory cytokine production by both murine and human DCs. Moreover, the DCs expressing the super stimulant are more potent to provoke both cellular and humoral immune responses against hepatitis C virus (HCV) antigen in vivo. Thus, the strategy capable of triggering and sustaining proinflammatory status of DCs may be used to boost efficiency of DC vaccine in preventing and combating the persistent infection of HCV or other chronic viruses.

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Section: Resultssupporting

confidence: 88%

A Super TLR Agonist to Improve Efficacy of Dendritic Cell Vaccine in Induction of Anti-HCV Immunity

et al. 2012

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“…The ChIP and RNApol ChIP procedures were performed according to Sandoval and co-workers [58], [59], and Rodriguez and co-workers [33], [60] with some modifications. Livers were surgically removed from anaesthetized animals, washed in PBS and fixed by immersion in 1% formaldehyde in PBS under rotation during 15 min at room temperature.…”

Section: Methodsmentioning

confidence: 99%

Epigenetic Transcriptional Regulation of the Growth Arrest-Specific gene 1 (Gas1) in Hepatic Cell Proliferation at Mononucleosomal Resolution

Sacilotto¹,

Espert²,

Castillo³

et al. 2011

PLoS ONE

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Background Gas1 (growth arrest-specific 1) gene is known to inhibit cell proliferation in a variety of models, but its possible implication in regulating quiescence in adult tissues has not been examined to date. The knowledge of how Gas1 is regulated in quiescence may contribute to understand the deregulation occurring in neoplastic diseases.Methodology/Principal Findings Gas1 expression has been studied in quiescent murine liver and during the naturally synchronized cell proliferation after partial hepatectomy. Chromatin immunoprecipitation at nucleosomal resolution (Nuc-ChIP) has been used to carry out the study preserving the in vivo conditions. Transcription has been assessed at real time by quantifying the presence of RNA polymerase II in coding regions (RNApol-ChIP). It has been found that Gas1 is expressed not only in quiescent liver but also at the cell cycle G1/S transition. The latter expression peak had not been previously reported. Two nucleosomes, flanking a nucleosome-free region, are positioned close to the transcription start site. Both nucleosomes slide in going from the active to the inactive state and vice versa. Nuc-ChIP analysis of the acquisition of histone epigenetic marks show distinctive features in both active states: H3K9ac and H3K4me2 are characteristic of transcription in G0 and H4R3me2 in G1/S transition. Sequential-ChIP analysis revealed that the “repressing” mark H3K9me2 colocalize with several “activating” marks at nucleosome N-1 when Gas1 is actively transcribed suggesting a greater plasticity of epigenetic marks than proposed until now. The recruitment of chromatin-remodeling or modifying complexes also displayed distinct characteristics in quiescence and the G1/S transition.Conclusions/SignificanceThe finding that Gas1 is transcribed at the G1/S transition suggests that the gene may exert a novel function during cell proliferation. Transcription of this gene is modulated by specific “activating” and “repressing” epigenetic marks, and by chromatin remodeling and histone modifying complexes recruitment, at specific nucleosomes in Gas1 promoter.

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“…Cerulein-induced pancreatitis might involve TNF signaling, since neutralization of TNF with the TNF blocker Etanercept attenuates cerulein-induced pancreas necrosis [105]. Moreover, the induction of inflammatory effectors such as IL-6 and iNOS is reduced in cerulein-treated TNF -/- mice [106]. Importantly, RIP3 -/- mice were also resistant to cerulein-induced pancreatitis [36, 37].…”

Section: Necrosis In Chemical- and Trauma-induced Cell Injurymentioning

confidence: 99%

Going up in flames: necrotic cell injury and inflammatory diseases

Challa

Chan

2010

Cell. Mol. Life Sci.

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Recent evidence indicates that cell death can be induced through multiple mechanisms. Strikingly, the same death signal can often induce apoptotic as well as non-apoptotic cell death. For instance, inhibition of caspases often converts an apoptotic stimulus to one that causes necrosis. Because a dedicated molecular circuitry distinct from that controlling apoptosis is required for necrotic cell injury, terms such as "programmed necrosis" or "necroptosis" have been used to distinguish stimulus-dependent necrosis from those induced by non-specific traumas (e.g. heat shock) or secondary necrosis induced as a consequence of apoptosis. In several experimental models, programmed necrosis/necroptosis has been shown to be a crucial control point for pathogen-or injury-induced inflammation. In this review, we will discuss the molecular mechanisms that regulate programmed necrosis/necroptosis and its biological significance in pathogen infections, drug-induced cell injury and trauma-induced tissue damage. Keywords RIP1; RIP3; programmed necrosis; inflammation; TNF Non-apoptotic cell death comes in different flavorsMetazoan homeostasis is achieved through balancing cell proliferation and cell death. The critical role of apoptosis is demonstrated by the many experiments where genetic ablation of components of the apoptosis pathway leads to blunted embryonic development. Work in recent years shows that cell death in multi-cellular organisms comes in many flavors. For instance, paraptosis is a form of non-apoptotic cell death marked by mitochondrial/ER swelling and vacuolation. It was first described as a form of neuronal cell death [1,2], but has recently been observed in certain tumors treated with the chemotherapeutic drug taxol [3]. Pyroptosis is characterized by potassium efflux and caspase-1 mediated activation of the inflammasome, and the rapid loss of plasma membrane integrity [4]. It is often activated during bacterial infections and thus is an important host defense against pathogens [5]. Autophagy, a cellular survival pathway in response to nutrient deprivation [6], has been shown to cause cell death in certain situations [7][8][9]. Although these non-apoptotic cell death pathways often exhibit overlapping morphological features, it is unclear if they also utilize similar molecular machineries to execute the demise of the cell. The term "necrosis" was once used to describe cell death from trauma such as that induced by heat shock or repeated cycles of freeze/thaw. In tissue culture, cells often undergo late stage "secondary necrosis" in response to apoptotic stimuli. This observation further contributed to the notion that necrosis is a by-product of apoptosis. However, it is now clear that necrosis can be triggered as a direct result of "extrinsic" stimulation by death cytokines in the TNF superfamily (e.g. TNF, Fas ligand (FasL) and TRAIL (TNF-related apoptosis inducing factor) [10]) or by "intrinsic" signals such as DNA damage [11,12]. Emerging evidence indicates that specific signaling pathways are requi...

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Ordered transcriptional factor recruitment and epigenetic regulation of tnf-α in necrotizing acute pancreatitis

Cited by 24 publications

References 53 publications

A Super TLR Agonist to Improve Efficacy of Dendritic Cell Vaccine in Induction of Anti-HCV Immunity

A Super TLR Agonist to Improve Efficacy of Dendritic Cell Vaccine in Induction of Anti-HCV Immunity

Epigenetic Transcriptional Regulation of the Growth Arrest-Specific gene 1 (Gas1) in Hepatic Cell Proliferation at Mononucleosomal Resolution

Going up in flames: necrotic cell injury and inflammatory diseases

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