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Macrophage HIF1

Sarah E Corcoran, Luke A J O'Neill
HIF1α is a common component of pathways involved in the control of cellular metabolism and has a role in regulating immune cell effector functions. Additionally, HIF1α is critical for the maturation of dendritic cells and for the activation of T cells. HIF1α is induced in LPS-activated macrophages, where it is critically involved in glycolysis and the induction of proinflammatory genes, notably Il1b. The mechanism of LPS-stimulated HIF1α induction involves succinate, which inhibits prolyl hydroxylases (PHDs)...
October 3, 2016: Journal of Clinical Investigation
Jérôme Cros, Emilie Sbidian, Katia Posseme, Alexia Letierce, Catherine Guettier, Gérard Benoît, Sophie Ferlicot
The behaviour of clear cell renal cell carcinoma (CCRCC) is highly unpredictable. Despite adequate initial surgery, 20 to 30 % of patients will develop local recurrence or metastasis during follow-up. Usual clinical and pathology parameters tend to classify most patients in an intermediate prognosis group, and molecular markers to determine prognosis more accurately are needed. A key feature of CCRCC is its abundant vascularization. Factors that upregulate angiogenesis, such as hypoxia and the presence of immune cells including macrophages, also modulate tumour proliferation and metastasis...
September 2016: Virchows Archiv: An International Journal of Pathology
Chorng-Kai Wen, Tzung-Yan Lee
BACKGROUND: Electroacupuncture (EA) shows anti-inflammation and several pleiotropic effects that interact with metabolic pathways. In the present study we tested the hypothesis that EA prevents inflammatory response and weight gain in obese mice through modulation of hypoxia-inducible factors-1α (HIF1-α)-dependent pathways in white adipose tissues. METHODS: Mice were divided in 4 groups: Non-obese, ob/ob, ob/ob submitted to 3 treatments, ob/ob submitted to 7 treatments...
2015: BMC Complementary and Alternative Medicine
Johannes Meiser, Lisa Krämer, Sean C Sapcariu, Nadia Battello, Jenny Ghelfi, Aymeric Fouquier D'Herouel, Alexander Skupin, Karsten Hiller
Upon stimulation with Th1 cytokines or bacterial lipopolysaccharides, resting macrophages shift their phenotype toward a pro-inflammatory state as part of the innate immune response. LPS-activated macrophages undergo profound metabolic changes to adapt to these new physiological requirements. One key step to mediate this metabolic adaptation is the stabilization of HIF1α, which leads to increased glycolysis and lactate release, as well as decreased oxygen consumption. HIF1 abundance can result in the induction of the gene encoding pyruvate dehydrogenase kinase 1 (PDK1), which inhibits pyruvate dehydrogenase (PDH) via phosphorylation...
February 19, 2016: Journal of Biological Chemistry
Benoît Thézé, Nicholas Bernards, Audrey Beynel, Stephan Bouet, Bertrand Kuhnast, Irène Buvat, Bertrand Tavitian, Raphaël Boisgard
BACKGROUND: Clinical studies implying the sunitinib multi-kinase inhibitor have led to disappointing results for breast cancer care but mostly focused on HER2-negative subtypes. Preclinical researches involving this drug mostly concern Triple Negative Breast Cancer (TNBC) murine models. Here, we explored the therapeutic efficacy of sunitinib on a PyMT-derived transplanted model classified as luminal B (HER2-positive) and monitored the response to treatment using both in vivo and ex vivo approaches...
2015: BMC Cancer
Albin Rudisch, Matthew Richard Dewhurst, Luminita Gabriela Horga, Nina Kramer, Nathalie Harrer, Meng Dong, Heiko van der Kuip, Andreas Wernitznig, Andreas Bernthaler, Helmut Dolznig, Wolfgang Sommergruber
We established co-cultures of invasive or non-invasive NSCLC cell lines and various types of fibroblasts (FBs) to more precisely characterize the molecular mechanism of tumor-stroma crosstalk in lung cancer. The HGF-MET-ERK1/2-CREB-axis was shown to contribute to the onset of the invasive phenotype of Calu-1 with HGF being secreted by FBs. Differential expression analysis of the respective mono- and co-cultures revealed an upregulation of NFκB-related genes exclusively in co-cultures with Calu-1. Cytokine Array- and ELISA-based characterization of the "cytokine fingerprints" identified CSF2 (GM-CSF), CXCL1, CXCL6, VEGF, IL6, RANTES and IL8 as being specifically upregulated in various co-cultures...
2015: PloS One
Agata Szade, Anna Grochot-Przeczek, Urszula Florczyk, Alicja Jozkowicz, Jozef Dulak
Blood vessel formation is a fundamental process for the development of organism and tissue regeneration. Of importance, angiogenesis occurring during postnatal development is usually connected with inflammation. Here, we review how molecular and cellular mechanisms underlying inflammatory reactions regulate angiogenesis. Inflamed tissues are characterized by hypoxic conditions and immune cell infiltration. In this review, we describe an interplay of hypoxia-inducible factors (HIFs), HIF1 and HIF2, as well as NF-κB and nitric oxide in the regulation of angiogenesis...
March 2015: IUBMB Life
Christophe Ravaud, David Esteve, Phi Villageois, Anne Bouloumie, Christian Dani, Annie Ladoux
Adipose tissue expansion is well-orchestrated to fulfill the energy demand. It results from adipocyte hypertrophy and hyperplasia due to adipose progenitor cell (APC) expansion and differentiation. Chronic low grade inflammation and hypoxia take place in obese adipose tissue microenvironment. Both of these events were shown to impact the APC pool by promoting increased self-renewal along with a decrease in the APC differentiation potential. However, no common target has been identified so far. Here we show that the immediate early response 3 gene (IER3) is preferentially expressed in APCs and is essential for APC proliferation and self-renewal...
August 2015: Stem Cells
Maxime Rotival, Jeong-Hun Ko, Prashant K Srivastava, Audrey Kerloc'h, Alex Montoya, Claudio Mauro, Peter Faull, Pedro R Cutillas, Enrico Petretto, Jacques Behmoaras
Macrophage multinucleation (MM) is essential for various biological processes such as osteoclast-mediated bone resorption and multinucleated giant cell-associated inflammatory reactions. Here we study the molecular pathways underlying multinucleation in the rat through an integrative approach combining MS-based quantitative phosphoproteomics (LC-MS/MS) and transcriptome (high-throughput RNA-sequencing) to identify new regulators of MM. We show that a strong metabolic shift toward HIF1-mediated glycolysis occurs at transcriptomic level during MM, together with modifications in phosphorylation of over 50 proteins including several ARF GTPase activators and polyphosphate inositol phosphatases...
March 2015: Molecular & Cellular Proteomics: MCP
Gabrielle C Lam, Michael V Sefton
A better understanding of the factors governing the vascularization of engineered tissues is crucial for their advancement as therapeutic platforms. Here, we studied the effect of implant volume and cell densities on the in vivo vascularization of modular engineered tissue constructs. Sub-millimeter collagen modules containing adipose-derived mesenchymal stromal cells (adMSC) and enveloped by human umbilical vein endothelial cells (HUVEC) were subcutaneously implanted in severe-combined immunodeficient mice with a beige-mutation (SCID-bg) mice...
February 2015: Tissue Engineering. Part A
Shweta Joshi, Alok R Singh, Muamera Zulcic, Donald L Durden
UNLABELLED: Tumor growth, progression, and response to the hypoxic tumor microenvironment involve the action of hypoxia-inducible transcription factors, HIF1 and HIF2. HIF is a heterodimeric transcription factor containing an inducible HIFα subunit and a constitutively expressed HIFβ subunit. The signaling pathways operational in macrophages regulating hypoxia-induced HIFα stabilization remain the subject of intense investigation. Here, it was discovered that the PTEN/PI3K/AKT signaling axis controls hypoxia-induced HIF1α (HIF1A) and HIF2α (EPAS1) stability in macrophages...
October 2014: Molecular Cancer Research: MCR
Colin E Evans, Steven P Grover, Prakash Saha, Julia Humphries, Jung-Whan Kim, Bijan Modarai, Alberto Smith
INTRODUCTION: The formation of new vascular channels within and around venous thrombus contributes to its resolution. Neovascularisation arising from the surrounding vein may facilitate this process. Treatment of cancer patients with anti-angiogenic agents can lead to increased incidence of venous thromboembolic events, but the effect of these agents on the processes that govern thrombus resolution are unclear. The aim of this study was to determine the effect of anti-angiogenic treatment with 2-methoxyestradiol (2ME) on (i) angiogenic response in the thrombosed vein and (ii) venous thrombus resolution...
September 2014: Thrombosis Research
Karim C El Kasmi, Steven C Pugliese, Suzette R Riddle, Jens M Poth, Aimee L Anderson, Maria G Frid, Min Li, Soni S Pullamsetti, Rajkumar Savai, Maria A Nagel, Mehdi A Fini, Brian B Graham, Rubin M Tuder, Jacob E Friedman, Holger K Eltzschig, Ronald J Sokol, Kurt R Stenmark
Macrophage accumulation is not only a characteristic hallmark but is also a critical component of pulmonary artery remodeling associated with pulmonary hypertension (PH). However, the cellular and molecular mechanisms that drive vascular macrophage activation and their functional phenotype remain poorly defined. Using multiple levels of in vivo (bovine and rat models of hypoxia-induced PH, together with human tissue samples) and in vitro (primary mouse, rat, and bovine macrophages, human monocytes, and primary human and bovine fibroblasts) approaches, we observed that adventitial fibroblasts derived from hypertensive pulmonary arteries (bovine and human) regulate macrophage activation...
July 15, 2014: Journal of Immunology: Official Journal of the American Association of Immunologists
Stefan Landgraeber, Marcus Jäger, Joshua J Jacobs, Nadim James Hallab
All of the over 1 million total joint replacements implanted in the US each year are expected to eventually fail after 15-25 years of use, due to slow progressive subtle inflammation at the bone implant interface. This inflammatory disease state is caused by implant debris acting, primarily, on innate immune cells, that is, macrophages. This slow progressive pathological bone loss or "aseptic loosening" is a potentially life-threatening condition due to the serious complications in older people (>75 yrs) of total joint replacement revision surgery...
2014: Mediators of Inflammation
Mehdi Metheni, Nadia Echebli, Marie Chaussepied, Céline Ransy, Christiane Chéreau, Kirsty Jensen, Elizabeth Glass, Frédéric Batteux, Frédéric Bouillaud, Gordon Langsley
Theileria annulata infects predominantly macrophages, and to a lesser extent B cells, and causes a widespread disease of cattle called tropical theileriosis. Disease-causing infected macrophages are aggressively invasive, but this virulence trait can be attenuated by long-term culture. Attenuated macrophages are used as live vaccines against tropical theileriosis and via their characterization one gains insights into what host cell trait is altered concomitant with loss of virulence. We established that sporozoite infection of monocytes rapidly induces hif1-α transcription and that constitutive induction of HIF-1α in transformed leukocytes is parasite-dependent...
February 2014: Cellular Microbiology
Linda Enns, Warren Ladiges
The concept that invasive cancer is associated with increased levels of reactive oxygen species (ROS) generated by mitochondria is consistent with an ROS-mediated signaling mechanism. As a tumor grows, it encounters adverse microenvironments, one of which is low oxygen (hypoxia), which selects tumor cells with characteristics of increased invasiveness. Hypoxic environments select for tumor cells with stabilized HIF1 apha, a transcription factor that regulates genes coding for pro-tumor cytokines that signal stromal cells such as macrophages and fibroblasts to support an invasive tumor cell phenotype...
December 2012: Journal of Bioenergetics and Biomembranes
Colin Edward Evans, Julia Humphries, Katherine Mattock, Matthew Waltham, Ashar Wadoodi, Prakash Saha, Bijan Modarai, Patrick H Maxwell, Patrick J Maxwell, Alberto Smith
OBJECTIVE: Angiogenic factors are expressed within thrombus during resolution, but the primary stimulus for neovascularization is unknown. Our aims were to determine whether (1) hypoxia and hypoxia-inducible factor 1α (HIF1α) are induced in resolving thrombus, (2) this stimulates angiogenic factor production, and (3) upregulating HIF1α enhances thrombus resolution and vein recanalization. METHODS AND RESULTS: Oxygen tension in the thrombus was negatively correlated with HIF1α levels (Spearman correlation [RS] = -0...
December 2010: Arteriosclerosis, Thrombosis, and Vascular Biology
Joseph Prandota
Approximately two billion people worldwide are chronically infected with T. gondii and yet with largely unknown consequences. On the other hand, several authors reported an association between migraine and patent foramen ovale (PFO), and different types of headaches, including migraine, may be precipitated by various diseased states or medications associated with marked immune irregularities, which sometimes cause reactivation of latent cerebral toxoplasmosis (CT). Recently, in a group of 104 subjects with migraine, 46 individuals (44...
February 2010: International Journal of Neuroscience
Deepak Darshan, Gregory J Anderson
The amount of iron in the plasma is determined by the regulated release of iron from most body cells, but macrophages, intestinal enterocytes and hepatocytes play a particularly important role in this process. This cellular iron efflux is modulated by the liver-derived peptide hepcidin, and this peptide is now regarded as the central regulator of body iron homeostasis. Hepcidin expression is influenced by systemic stimuli such as iron stores, the rate of erythropoiesis, inflammation, hypoxia and oxidative stress...
February 2009: Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
Judith C Sluimer, Jean-Marie Gasc, Job L van Wanroij, Natasja Kisters, Mathijs Groeneweg, Maarten D Sollewijn Gelpke, Jack P Cleutjens, Luc H van den Akker, Pierre Corvol, Bradly G Wouters, Mat J Daemen, Ann-Pascale J Bijnens
OBJECTIVES: We sought to examine the presence of hypoxia in human carotid atherosclerosis and its association with hypoxia-inducible transcription factor (HIF) and intraplaque angiogenesis. BACKGROUND: Atherosclerotic plaques develop intraplaque angiogenesis, which is a typical feature of hypoxic tissue and expression of HIF. METHODS: To examine the presence of hypoxia in atherosclerotic plaques, the hypoxia marker pimonidazole was infused before carotid endarterectomy in 7 symptomatic patients...
April 1, 2008: Journal of the American College of Cardiology
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