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Macrophage HIF1

Rocio García-Pérez, Joana Ferrer Fábrega, Aranzazu Varona-Bosque, Carlos Manuel Martínez, Beatriz Revilla-Nuin, Laia Cabellos, Romina Pena, Ramón Vilana, Carolina Gonzalez-Abós, Juan Carlos García-Valdecasas, José Fuster Obregón
Associated liver partition and portal vein ligation for staged hepatectomy (ALPPS) has been suggested as a potential therapy for extensive bilobar liver tumors, although in some circumstances this technique may induce tumor progression, a fact still not well studied. Our aim was to study tumor hepatic progression induced by the first step of ALPPS in a WAG/Rij rat syngenic model of metastatic colorectal carcinoma by subcapsular CC531 cell line inoculation. ALPPS induced: tumor progression on deportalized lobe and metastases; expression of hepatic vasculogenic factors (HIF1-α and VEGF); and a dramatic increase of Kupffer cells (KCs) and tumor-associated macrophages (TAMs)...
May 24, 2018: Scientific Reports
Song-Yang Zhang, Yong-Qiang Dong, Pengcheng Wang, Xingzhong Zhang, Yu Yan, Lulu Sun, Bo Liu, Dafang Zhang, Heng Zhang, Huiying Liu, Wei Kong, Gang Hu, Yatrik M Shah, Frank J Gonzalez, Xian Wang, Changtao Jiang
The adipose Nod-like receptor protein 3 (NLRP3) inflammasome senses danger-associated molecular patterns (DAMPs) and initiates insulin resistance, but the mechanisms of adipose inflammasome activation remains elusive. In this study, Homocysteine (Hcy) is revealed to be a DAMP that activates adipocyte NLRP3 inflammasomes, participating in insulin resistance. Hcy-induced activation of NLRP3 inflammasomes were observed in both adipocytes and adipose tissue macrophages (ATMs) and mediated insulin resistance. Lysophosphatidylcholine (lyso-PC) acted as a second signal activator, mediating Hcy-induced adipocyte NLRP3 inflammasome activation...
April 27, 2018: EBioMedicine
Richa Shrivastava, Varsha Singh, Mohammad Asif, Mahendra Pal Singh Negi, Smrati Bhadauria
AIMS: HIF is an important transcription-regulator for adaptation to cellular stress in cells of myeloid origin. Classically, expression and activity of HIF1-α is regulated by oxygen-concentration within cell. However, there exists an alternative regulatory mechanism affecting HIF1-α levels independent of oxygen concentration particularly in inflammatory cells like macrophages. Here we report the mechanism of HIF1-α upregulation in TAMs by Oncostatin-M (OSM) independent of cellular oxygen concentration...
February 1, 2018: Life Sciences
Iuliana Nenu, Grigore-Aristide Gafencu, Tiberiu Popescu, Gabriel Kacso
Prostate cancer, one of the most common male malignancies with an increasing incidence in the recent years, requires the development of new methods of treatment. One of the most debated subjects is the tumor-associated macrophages (TAM). Although, the pathophysiological mechanisms are still a subject of intense research, TAM acts as procarcinogenic factors. It was also demonstrated that hypoxia-inducible factor 1 (HIF1) induces the expression of TAM genes involved in prostate carcinogenesis. Furthermore, it should be noted that the stromal extracellular lactate, the result of tumoral glycolysis process is one of the HIF1 activators...
July 2017: Journal of Cancer Research and Therapeutics
Rossana Cecchi, Barbara Muciaccia, Costantino Ciallella, Natale Mario Di Luca, Akihiko Kimura, Cristina Sestili, Mizuho Nosaka, Toshikazu Kondo
BACKGROUND: Several fatal cases of bodybuilders, following a myocardial infarction after long exposure to androgenic-anabolic steroids (AAS), are reported. In recent years, evidence has emerged of cases of heart failure related to AAS consumption, with no signs of coronary or aorta atherosclerosis. This study aims to further investigate the pathogenesis of the ventricular AAS-related remodeling performing immunohistochemistry (IHC). METHOD: In order to examine innate immunity activity and myocytes and endothelial cell apoptosis, IHC analyses were performed on heart tissue of two cases of bodybuilders who died after years of supratherapeutic use of metelonone and nandrolone and where no atherosclerosis or thrombosis were found, using the following antibodies: anti-CD68, anti-iNOS, anti-CD163, anti-CD 15, anti-CD8, anti-CD4, anti-HIF1 α, and in situ TUNEL staining...
April 21, 2017: International Journal of Legal Medicine
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...
July 22, 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
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