610 Medizin und Gesundheit
Refine
Year of publication
Document Type
- Article (93)
Language
- English (93)
Has Fulltext
- yes (93)
Is part of the Bibliography
- no (93)
Keywords
- inflammation (16)
- macrophage (14)
- cancer (7)
- breast cancer (6)
- macrophages (6)
- apoptosis (5)
- macrophage polarization (5)
- sphingosine-1-phosphate (5)
- hypoxia (4)
- lipocalin-2 (4)
- microRNA (4)
- mitochondria (4)
- reactive oxygen species (4)
- tumor microenvironment (4)
- Hypoxia (3)
- Macrophages (3)
- RNA therapeutics (3)
- iron (3)
- lipoxygenase (3)
- psoriasis (3)
- tumor-associated macrophages (3)
- ATP-citrate lyase (2)
- Breast cancer (2)
- Breast tumors (2)
- Cancer (2)
- Chronic inflammation (2)
- HIF (2)
- IL-1β (2)
- Immunology (2)
- Inflammation (2)
- Iron (2)
- Messenger RNA (2)
- Mitochondria (2)
- Mitochondrial ROS (2)
- Nrf2 (2)
- ROS (2)
- acetyl-CoA (2)
- angiogenesis (2)
- atherosclerosis (2)
- chemotherapy (2)
- cholesterol (2)
- endoplasmic reticulum (2)
- gene expression (2)
- histone acetylation (2)
- immunity (2)
- interleukin-4 (2)
- metabolism (2)
- monocytes (2)
- pain (2)
- phagocytosis (2)
- proliferation (2)
- prostaglandins (2)
- renal cell carcinoma (2)
- resolution (2)
- sepsis (2)
- tumor progression (2)
- 5' UTR (1)
- AMP-activated kinase (AMPK) (1)
- ASCT (1)
- AU-rich element (1)
- Acute inflammation (1)
- BIAM-switch (1)
- CD36 (1)
- CD40 (1)
- CHIP (1)
- CYP1A1 (1)
- Cell binding (1)
- Cell death (1)
- Cell death and immune response (1)
- Cell signalling (1)
- Cell staining (1)
- Cellular stress responses (1)
- Complex II (1)
- Cytoskeleton (1)
- DNA damage (1)
- ER stress (1)
- Erythrophagocytosis (1)
- Extracellular vesicles (1)
- FTMT (1)
- Ferritinophagy (1)
- Ferroptosis (1)
- Flow cytometry (1)
- G2A (1)
- GEMs (1)
- GPCR (1)
- GRAND-SLAM (1)
- Gene expression (1)
- Gene prediction (1)
- Gene/Regulation (1)
- Genome annotation (1)
- Glycolysis (1)
- HAI‐1 (1)
- HCC marker (1)
- HDAC (1)
- HGF (1)
- HIF-1α (1)
- HIF-2 (1)
- HIF-2α (1)
- Hepatocellular carcinoma (1)
- Hypoxia inducible factor (1)
- IFN-β (1)
- IL-27 cytokine (1)
- ISR (1)
- Immune cells (1)
- JNK (1)
- Kinases (1)
- Kupffer cells (1)
- LDHB (1)
- LDL (1)
- Lipid peroxidation (1)
- Lipid signalling (1)
- MMP9 (1)
- Macrophage (1)
- Mild hypoxia (1)
- Monocytes and macrophages (1)
- Mouse models (1)
- Mφs (1)
- NADPH oxidase (1)
- NASH (1)
- NCOA4 (1)
- NLRP3 inflammasomes (1)
- Oxidative phosphorylation (1)
- PD-L1 (1)
- PDPK1 (1)
- PPTC7 (1)
- PTEN inducible kinase 1 (1)
- Parkinson's disease (1)
- Peritoneal macrophages (1)
- Physiology (1)
- Protein translation (1)
- RNA extraction (1)
- RNA isolation (1)
- RNA sequencing (1)
- RNA stability (1)
- RNA therapy (1)
- RNA-binding protein (1)
- RNA/MicroRNA (1)
- Receptors/Nuclear (1)
- Respiratory chain (1)
- Ribosomes (1)
- S1PR1 (1)
- S1PR4 (1)
- SDH (1)
- SLAM-seq (1)
- SLC7A11 (1)
- SPM (1)
- STAT1 (1)
- Sterols (1)
- T cells (1)
- TMEM126B (1)
- Transcription (1)
- Translation initiation (1)
- UPR (1)
- Zymosan-induced peritonitis (1)
- acute inflammation (1)
- adipose-derived stem cells (ASCs) (1)
- alcoholic hepatitis (1)
- alpha-synuclein (1)
- antioxidants (1)
- arachidonate 12/15-lipoxygenase (Alox12/15) (1)
- arachidonate 15-lipoxygenase (1)
- arachidonic acid (AA) (1)
- asparaginyl endopepdidase (AEP) (1)
- astrocytes (1)
- autologous stem cell transplantation (1)
- breast tumor (1)
- cancer cell metabolism (1)
- cancer metastases (1)
- cancer-associated fibroblasts (1)
- carcinoma (1)
- chelation therapy (1)
- chemokine (1)
- chronic hypoxia (1)
- chronic myeloid leukemia (1)
- clonal dominance (1)
- clonal hematopoiesis (1)
- complex I (1)
- costimulation (1)
- cytokine (1)
- cytokine, angiogenesis (1)
- cytotoxic T cells (1)
- cytotoxic lymphocytes (1)
- cytotoxicity (1)
- de novo transcription (1)
- diabetic nephropathy (1)
- differentiation (1)
- drug discovery (1)
- efferocytosis (1)
- electron transport chain (1)
- electrophiles (1)
- endothelial cell (1)
- epigenetic (1)
- erastin (1)
- exosome (1)
- exosomes (1)
- extracellular signal-regulated kinase (1)
- fatty acid (1)
- fatty acids (1)
- ferroportin (1)
- ferroptosis (1)
- fibrosarcoma (1)
- flow cytometry (1)
- gene signature (1)
- glucosylceramides (1)
- glutamine (1)
- glycolysis (1)
- hematopoietic stem cells (1)
- hematopoietic stress (1)
- hierarchical clustering (1)
- immune checkpoint (1)
- immunotherapy (1)
- infection (1)
- innate immunity (1)
- inflammation (1)
- iron chelator (1)
- iron chelators (1)
- iron homeostasis (1)
- iron metabolism (1)
- iron-trafficking (1)
- legumain (1)
- leukemia (1)
- lipid mediator (1)
- lipid metabolism (1)
- lipids (1)
- lipoproteins (1)
- lipoxin A4 (1)
- liver (1)
- liver X receptor (1)
- lung cancer (1)
- lung tumor heterogeneity (1)
- lymphangiogenesis (1)
- mRNA stability (1)
- mTOR (1)
- mammary cancer (1)
- mammary carcinoma (1)
- mast cells (1)
- metabolic reprogramming (1)
- miR (1)
- miR-375 (1)
- miR-6862-5p (1)
- miRNA let-7e (1)
- microenvironment (1)
- migration (1)
- mitochondrial dynamics (1)
- mitochondrial respiration (1)
- multiple myeloma (1)
- multispectral flow cytometry (1)
- natural killer T cells (1)
- nuclear factor 2 (erythroid-derived 2-like factor) (NFE2L2) (Nrf2) (1)
- oxidative stress (1)
- oxidized low density lipoprotein (1)
- p-eIF2α (1)
- p53 (1)
- peritoneal macrophages (1)
- peroxisome proliferator-activated receptor (1)
- polarization (1)
- polyunsaturated fatty acid (1)
- post-transcriptional regulation (1)
- prostacyclin (1)
- prostaglandin (1)
- protein-protein interaction (1)
- proteomics (1)
- resolution of inflammation (1)
- resolution of inflammation (1)
- resveratrol (1)
- sensory loss (1)
- signal transduction (1)
- somatic mutations (1)
- specialized pro-resolving lipid mediators (SPMs) (1)
- specialized pro-resolving mediator (1)
- sphingolipids (1)
- sterol regulatory element binding protein-2 (1)
- thromboxane (1)
- toll-like receptor (1)
- transcription (1)
- transcription factor (1)
- transcriptional profiling (1)
- transcriptome (1)
- tumor stroma (1)
- tumor-associated macrophages (TAM) (1)
- tumor‐associated macrophages (1)
- type B (1)
- tyrosine kinase inhibitors. (1)
- xenobiotics (1)
- zymosan (1)
Institute
- Medizin (92)
- Sonderforschungsbereiche / Forschungskollegs (33)
- Biochemie und Chemie (10)
- Zentrum für Arzneimittelforschung, Entwicklung und Sicherheit (ZAFES) (6)
- Biochemie, Chemie und Pharmazie (3)
- Exzellenzcluster Makromolekulare Komplexe (2)
- Pharmazie (2)
- Biowissenschaften (1)
- Buchmann Institut für Molekulare Lebenswissenschaften (BMLS) (1)
- Institut für Ökologie, Evolution und Diversität (1)
Highlights
• TAM polarization induces CP RNA.
• CP RNA expression is regulated by HIF-2 and STAT1.
• CP RNA is transferred from TAMs to HT1080 cells.
• CP RNA is translated by HT1080 cells and protects from ferroptosis.
• Co-cultured HT1080 cells decrease iron and lipid peroxidation.
Abstract
Solid tumors are characterized by hypoxic areas, which are prone for macrophage infiltration. Once infiltrated, macrophages polarize to tumor associated macrophages (TAM) to support tumor progression. Therefore, the crosstalk between TAMs and tumor cells is of current interest for the development of novel therapeutic strategies. These may comprise induction of an iron- and lipid peroxidation-dependent form of cell death, known as ferroptosis. To study the macrophage - tumor cell crosstalk we polarized primary human macrophages towards a TAM-like phenotype, co-cultured them with HT1080 fibrosarcoma cells, and analyzed the tumor cell response to ferroptosis induction. In TAMs the expression of ceruloplasmin mRNA increased, which was driven by hypoxia inducible factor 2 and signal transducer and activator of transcription 1. Subsequently, ceruloplasmin mRNA was transferred from TAMs to HT1080 cells via extracellular vesicles. In tumor cells, mRNA was translated into protein to protect HT1080 cells from RSL3-induced ferroptosis. Mechanistically this was based on reduced iron abundance and lipid peroxidation. Interestingly, in naïve macrophages also hypoxia induced ceruloplasmin under hypoxia and a co-culture of HT1080 cells with hypoxic macrophages recapitulated the protective effect observed in TAM co-cultures. In conclusion, TAMs provoke tumor cells to release iron and thereby protect them from lipid peroxidation/ferroptosis.
uORF-tools—workflow for the determination of translation-regulatory upstream open reading frames
(2019)
Ribosome profiling (ribo-seq) provides a means to analyze active translation by determining ribosome occupancy in a transcriptome-wide manner. The vast majority of ribosome protected fragments (RPFs) resides within the protein-coding sequence of mRNAs. However, commonly reads are also found within the transcript leader sequence (TLS) (aka 5’ untranslated region) preceding the main open reading frame (ORF), indicating the translation of regulatory upstream ORFs (uORFs). Here, we present a workflow for the identification of translation-regulatory uORFs. Specifically, uORF-Tools uses Ribo-TISH to identify uORFs within a given dataset and generates a uORF annotation file. In addition, a comprehensive human uORF annotation file, based on 35 ribo-seq files, is provided, which can serve as an alternative input file for the workflow. To assess the translation-regulatory activity of the uORFs, stimulus-induced changes in the ratio of the RPFs residing in the main ORFs relative to those found in the associated uORFs are determined. The resulting output file allows for the easy identification of candidate uORFs, which have translation-inhibitory effects on their associated main ORFs. uORF-Tools is available as a free and open Snakemake workflow at https://github.com/Biochemistry1-FFM/uORF-Tools. It is easily installed and all necessary tools are provided in a version-controlled manner, which also ensures lasting usability. uORF-Tools is designed for intuitive use and requires only limited computing times and resources.
In ischemic vascular diseases, leukocyte recruitment and polarization are crucial for revascularization and tissue repair. We investigated the role of vasodilator-stimulated phosphoprotein (VASP) in vascular repair. After hindlimb ischemia induction, blood flow recovery, angiogenesis, arteriogenesis, and leukocyte infiltration into ischemic muscles in VASP−/− mice were accelerated. VASP deficiency also elevated the polarization of the macrophages through increased signal transducer and activator of transcription (STAT) signaling, which augmented the release of chemokines, cytokines, and growth factors to promote leukocyte recruitment and vascular repair. Importantly, VASP deletion in bone marrow–derived cells was sufficient to mimic the increased blood flow recovery of global VASP−/− mice. In chemotaxis experiments, VASP−/− neutrophils/monocytes were significantly more responsive to M1-related chemokines than wild-type controls. Mechanistically, VASP formed complexes with the chemokine receptor CCR2 and β-arrestin-2, and CCR2 receptor internalization was significantly reduced in VASP−/− leukocytes. Our data indicate that VASP is a major regulator of leukocyte recruitment and polarization in postischemic revascularization and support a novel role of VASP in chemokine receptor trafficking.