365 results match your criteria: "Institute of General Physiology.[Affiliation]"
Int J Mol Sci
June 2019
Institute of General Physiology, Ulm University, Albert-Einstein-Allee 11, 89081 Ulm, Germany.
Interleukin-13 (IL-13) drives symptoms in asthma with high levels of T-helper type 2 cells (T2-cells). Since tight junctions (TJ) constitute the epithelial diffusion barrier, we investigated the effect of IL-13 on TJ in human tracheal epithelial cells. We observed that IL-13 increases paracellular permeability, changes claudin expression pattern and induces intracellular aggregation of the TJ proteins zonlua occludens protein 1, as well as claudins.
View Article and Find Full Text PDFBrain Behav Immun
August 2019
Laboratory for Molecular Psychosomatics, Department of Psychosomatic Medicine and Psychotherapy, University of Ulm, Ulm, Germany. Electronic address:
Cardiovascular disorders (CVD) and posttraumatic stress disorder (PTSD) are highly comorbid, but the underlying mechanisms are not fully understood. Chronic psychosocial stress was induced in male mice by chronic subordinate colony housing (CSC), a pre-clinically validated mouse model for PTSD. Cardiac structure and function were assessed on day 20 of the CSC paradigm.
View Article and Find Full Text PDFRespir Res
May 2019
Immunology & Respiratory Diseases Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Straße 65, 88397, Biberach an der Riss, Germany.
Background: Idiopathic pulmonary fibrosis (IPF) is a fatal respiratory disease characterized by aberrant fibroblast activation and progressive fibrotic remodelling of the lungs. Though the exact pathophysiological mechanisms of IPF remain unknown, TGF-β1 is thought to act as a main driver of the disease by mediating fibroblast-to-myofibroblast transformation (FMT). Recent reports have indicated that a metabolic shift towards aerobic glycolysis takes place during FMT and that metabolic shifts can directly influence aberrant cell function.
View Article and Find Full Text PDFCurr Opin Pharmacol
August 2019
Institute of General Physiology, University of Ulm, Ulm, Germany.
Similar to other members of the P2X receptor family, the P2X4 receptor at the plasma membrane forms a highly Ca permeable, non-selective cation channel that is activated by extracellular ATP. Yet, P2X4 differs from the other subtypes, as it is predominantly localized on late endosomal, lysosomal and/or lysosome-related organelles. It is targeted there by virtue of tyrosine-based and di-leucine like trafficking motifs contained within its C-terminal and N-terminal regions respectively.
View Article and Find Full Text PDFFASEB J
April 2019
Institute of Pharmacology and Toxicology, University of Ulm Medical Center, Ulm, Germany.
The antibiotic bacitracin (Bac) inhibits cell wall synthesis of gram-positive bacteria. Here, we discovered a totally different activity of Bac: the neutralization of bacterial exotoxins. Bac prevented intoxication of mammalian cells with the binary enterotoxins Clostridium botulinum C2, C.
View Article and Find Full Text PDFNeoplasia
February 2019
Department of General Thoracic Surgery, Inselspital, Bern University Hospital, University of Bern, Switzerland; Department of BioMedical Research (DBMR), University of Bern, Switzerland. Electronic address:
Cell lines are essential tools to standardize and compare experimental findings in basic and translational cancer research. The current dogma states that cancer stem cells feature an increased tumor initiation capacity and are also chemoresistant. Here, we identified and comprehensively characterized three morphologically distinct cellular subtypes in the non-small cell lung cancer cell line A549 and challenge the current cancer stem cell dogma.
View Article and Find Full Text PDFPflugers Arch
April 2019
Institute of General Physiology, Ulm University, Albert-Einstein-Allee 11, 89081, Ulm, Germany.
The lung is the interface between air and blood where the exchange of oxygen and carbon dioxide occurs. The surface liquid that is directly exposed to the gaseous compartment covers both conducting airways and respiratory zone and forms the air-liquid interface. The barrier that separates this lining fluid of the airways and alveoli from the extracellular compartment is the pulmonary epithelium.
View Article and Find Full Text PDFAm J Physiol Lung Cell Mol Physiol
January 2019
Institute of General Physiology, Ulm University, Ulm , Germany.
Mucus clearance provides an essential innate defense mechanism to keep the airways and lungs free of particles and pathogens. Baseline and stimulated mucin secretion from secretory airway epithelial cells need to be tightly regulated to prevent mucus hypersecretion and mucus plugging of the airways. It is well established that extracellular ATP is a potent stimulus for regulated mucus secretion.
View Article and Find Full Text PDFPLoS One
March 2019
Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom.
A range of cellular functions have been attributed to caveolae, flask-like invaginations of the plasma membrane. Here, we have used RNA-seq to achieve quantitative transcriptional profiling of primary embryonic fibroblasts from caveolin 1 knockout mice (CAV1-/- MEFs), and thereby to gain hypothesis-free insight into how these cells respond to the absence of caveolae. Components of the extracellular matrix were decisively over-represented within the set of genes displaying altered expression in CAV1-/- MEFs when compared to congenic wild-type controls.
View Article and Find Full Text PDFSci Rep
September 2018
ARTORG Center for Biomedical Engineering Research, Organs-on-Chip Technologies, University of Bern, Bern, Switzerland.
Organs-on-chips have the potential to improve drug development efficiency and decrease the need for animal testing. For the successful integration of these devices in research and industry, they must reproduce in vivo contexts as closely as possible and be easy to use. Here, we describe a 'breathing' lung-on-chip array equipped with a passive medium exchange mechanism that provide an in vivo-like environment to primary human lung alveolar cells (hAEpCs) and primary lung endothelial cells.
View Article and Find Full Text PDFRe-sensitization of P2X receptors depends on a protonation/de-protonation cycle Protonation and de-protonation of the receptors is achieved by internalization and recycling of P2X receptors via acidic compartments Protonation and de-protonation occurs at critical histidine residues within the extracellular loop of P2X receptors Re-sensitization is blocked in the presence of the receptor agonist ATP ABSTRACT: P2X receptors are members of the P2X receptor family of cation-permeable, ligand-gated ion channels that open in response to the binding of extracellular ATP. P2X receptors are implicated in a variety of biological processes, including cardiac function, cell death, pain sensation and immune responses. These physiological functions depend on receptor activation on the cell surface.
View Article and Find Full Text PDFMediators Inflamm
October 2018
Institute of Clinical and Experimental Trauma-Immunology, University Hospital Ulm, 89081 Ulm, Germany.
Background: Polymorphonuclear granulocytes (PMN) play a crucial role in host defense. Physiologically, exposure of PMN to the complement activation product C5a results in a protective response against pathogens, whereas in the case of systemic inflammation, excessive C5a substantially impairs neutrophil functions. To further elucidate the inability of PMN to properly respond to C5a, this study investigates the role of the cellular membrane potential of PMN in response to C5a.
View Article and Find Full Text PDFFASEB J
August 2018
Department of Biochemistry and Molecular Biology, Faculty of Biology, Complutense University, Madrid, Spain.
The release of pulmonary surfactant by alveolar type II (ATII) cells is essential for lowering surface tension at the respiratory air-liquid interface, stabilizing the lungs against physical forces tending to alveolar collapse. Hydrophobic surfactant protein (SP)-B ensures the proper packing of newly synthesized surfactant particles, promotes the formation of the surface active film at the alveolar air-liquid interface and maintains its proper structure along the respiratory dynamics. We report that membrane-associated SP-B efficiently induces secretion of pulmonary surfactant by ATII cells, at the same level as potent secretagogues such as ATP.
View Article and Find Full Text PDFBMC Cancer
February 2018
Department of General and Visceral Surgery, Ulm University Hospital, Albert-Einstein-Allee 23, 89081, Ulm, Germany.
Background: Colorectal cancer (CRC) is the fourth leading cause of cancer related deaths worldwide and prognosis in advanced tumor stage still remains poor. Since CK1 isoforms have been reported to be deregulated in several tumor entities CK1 has emerged as a novel drug target in cancer therapy. In this study we set out to investigate whether CK1α might have the potential to serve as prognostic marker.
View Article and Find Full Text PDFACS Nano
February 2018
INSERM, UMR U1152, Laboratoire d'Excellence Inflamex, Département Hospitalo-Universitaire FIRE (Fibrosis, Inflammation, and Remodeling), University Paris Diderot, Sorbonne Paris Cité, 75018 Paris, France.
Silver nanoparticles (AgNPs) are microbicidal agents which could be potentially used as an alternative to antivirals to treat human infectious diseases, especially influenza virus infections where antivirals have generally proven unsuccessful. However, concerns about the use of AgNPs on humans arise from their potential toxicity, although mechanisms are not well-understood. We show here, in the context of an influenza virus infection of lung epithelial cells, that AgNPs down-regulated influenza induced CCL-5 and -IFN-β release (two cytokines important in antiviral immunity) through RIG-I inhibition, while enhancing IL-8 production, a cytokine important for mobilizing host antibacterial responses.
View Article and Find Full Text PDFBiochim Biophys Acta Biomembr
May 2018
Institute of General Physiology, University of Ulm, Albert-Einstein-Allee 11, D-89081 Ulm, Germany.
In alveolar type II (AT II) cells, pulmonary surfactant (PS) is synthetized, stored and exocytosed from lamellar bodies (LBs), specialized large secretory organelles. By applying polarization microscopy (PM), we confirm a specific optical anisotropy of LBs, which indicates a liquid-crystalline mesophase of the stored surfactant phospholipids (PL) and an unusual case of a radiation-symmetric, spherocrystalline organelle. Evidence is shown that the degree of anisotropy is dependent on the amount of lipid layers and their degree of hydration, but unaffected by acutely modulating vital cell parameters like intravesicular pH or cellular energy supply.
View Article and Find Full Text PDFJ Gen Physiol
February 2018
Institute of General Physiology, Ulm University, Ulm, Germany
Vesicular P2X receptors are known to facilitate secretion and activation of pulmonary surfactant in the alveoli of the lungs. P2X receptors are expressed in the membrane of lamellar bodies (LBs), large secretory lysosomes that store lung surfactant in alveolar type II epithelial cells, and become inserted into the plasma membrane after exocytosis. Subsequent activation of P2X receptors by adenosine triphosphate (ATP) results in local fusion-activated cation entry (FACE), facilitating fusion pore dilation, surfactant secretion, and surfactant activation.
View Article and Find Full Text PDFJ Virol
January 2018
Institute of Virology, Ulm University Medical Center, Ulm, Germany
The human cytomegalovirus (HCMV) tegument protein pUL71 is required for efficient secondary envelopment and accumulates at the Golgi compartment-derived viral assembly complex (vAC) during infection. Analysis of various C-terminally truncated pUL71 proteins fused to enhanced green fluorescent protein (eGFP) identified amino acids 23 to 34 as important determinants for its Golgi complex localization. Sequence analysis and mutational verification revealed the presence of an N-terminal tyrosine-based trafficking motif (YXXΦ) in pUL71.
View Article and Find Full Text PDFSci Rep
June 2017
Institute of Pharmacology and Toxicology, University of Ulm Medical Center, 89081, Ulm, Germany.
Binary enterotoxins Clostridium (C.) botulinum C2 toxin, C. perfringens iota toxin and C.
View Article and Find Full Text PDFSci Rep
April 2017
Institute of Pharmacology and Toxicology, University of Ulm Medical Center, Ulm, Germany.
Diphtheria toxin kills human cells because it delivers its enzyme domain DTA into their cytosol where it inhibits protein synthesis. After receptor-mediated uptake of the toxin, DTA translocates from acidic endosomes into the cytosol, which might be assisted by host cell factors. Here we investigated the role of Hsp90 and its co-chaperones during the uptake of native diphtheria toxin into human cells and identified the components of the Hsp90 machinery including Hsp90, Hsp70, Cyp40 and the FK506 binding proteins FKBP51 and FKBP52 as DTA binding partners.
View Article and Find Full Text PDFInvest New Drugs
June 2017
Department of Anesthesiology, University Hospital of Ulm, Albert-Einstein-Allee 23, D-89075, Ulm, Germany.
Background and Purpose IC261 (3-[(2,4,6-trimethoxyphenyl)methylidenyl]-indolin-2-one) has previously been introduced as an isoform specific inhibitor of casein kinase 1 (CK1) causing cell cycle arrest or cell death of established tumor cell lines. However, it is reasonable to assume that not all antitumor activities of IC261 are mediated by the inhibition of CK1. Meanwhile there is growing evidence that functional voltage-gated sodium channels are also implicated in the progression of tumors as their blockage suppresses tumor migration and invasion of different tumor cell lines.
View Article and Find Full Text PDFPflugers Arch
January 2017
Institute of General Physiology, Ulm University, Albert-Einstein-Allee 11, 89081, Ulm, Germany.
Inflammatory lung diseases like asthma bronchiale, chronic obstructive pulmonary disease and allergic airway inflammation are widespread public diseases that constitute an enormous burden to the health systems. Mainly classified as inflammatory diseases, the treatment focuses on strategies interfering with local inflammatory responses by the immune system. Inflammatory lung diseases predispose patients to severe lung failures like alveolar oedema, respiratory distress syndrome and acute lung injury.
View Article and Find Full Text PDFAm J Respir Cell Mol Biol
March 2017
1 Institute of General Physiology, Ulm University, Ulm, Germany.
J Neurochem
October 2016
Institute of Molecular and Cellular Anatomy, Ulm University, Ulm, Germany.
Rho GTPases play prominent roles in the regulation of cytoskeletal reorganization. Many aspects have been elaborated concerning the individual functions of Rho GTPases in distinct signaling pathways leading to cytoskeletal rearrangements. However, major questions have yet to be answered regarding the integration and the signaling hierarchy of different Rho GTPases in regulating the cytoskeleton in fundamental physiological events like neuronal process differentiation.
View Article and Find Full Text PDFBiochim Biophys Acta
August 2016
Department of Physiology and Medical Physics, Division of Physiology, Medical University of Innsbruck, Schöpfstraße 41, 6020 Innsbruck, Austria.
The molecular basis involving adsorption of pulmonary surfactant at the respiratory air-liquid interface and the specific roles of the surfactant proteins SP-B and SP-C in this process have not been completely resolved. The reasons might be found in the largely unknown structural assembly in which surfactant lipids and proteins are released from alveolar type II cells, and the difficulties to sample, manipulate and visualize the adsorption of these micron-sized particles at an air-liquid interface under appropriate physiological conditions. Here, we introduce several approaches to overcome these problems.
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