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  1. Article ; Online: Dendritic Cells and CCR7 Expression

    Emma Probst Brandum / Astrid Sissel Jørgensen / Mette Marie Rosenkilde / Gertrud Malene Hjortø

    International Journal of Molecular Sciences, Vol 22, Iss 8340, p

    An Important Factor for Autoimmune Diseases, Chronic Inflammation, and Cancer

    2021  Volume 8340

    Abstract: Chemotactic cytokines—chemokines—control immune cell migration in the process of initiation and resolution of inflammatory conditions as part of the body’s defense system. Many chemokines also participate in pathological processes leading up to and ... ...

    Abstract Chemotactic cytokines—chemokines—control immune cell migration in the process of initiation and resolution of inflammatory conditions as part of the body’s defense system. Many chemokines also participate in pathological processes leading up to and exacerbating the inflammatory state characterizing chronic inflammatory diseases. In this review, we discuss the role of dendritic cells (DCs) and the central chemokine receptor CCR7 in the initiation and sustainment of selected chronic inflammatory diseases: multiple sclerosis (MS), rheumatoid arthritis (RA), and psoriasis. We revisit the binary role that CCR7 plays in combatting and progressing cancer, and we discuss how CCR7 and DCs can be harnessed for the treatment of cancer. To provide the necessary background, we review the differential roles of the natural ligands of CCR7, CCL19, and CCL21 and how they direct the mobilization of activated DCs to lymphoid organs and control the formation of associated lymphoid tissues (ALTs). We provide an overview of DC subsets and, briefly, elaborate on the different T-cell effector types generated upon DC–T cell priming. In the conclusion, we promote CCR7 as a possible target of future drugs with an antagonistic effect to reduce inflammation in chronic inflammatory diseases and an agonistic effect for boosting the reactivation of the immune system against cancer in cell-based and/or immune checkpoint inhibitor (ICI)-based anti-cancer therapy.
    Keywords dendritic cell ; CCR7 ; chronic inflammation ; MS ; RA ; psoriasis ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 616 ; 610
    Language English
    Publishing date 2021-08-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Reply to

    Trine L. Toft-Bertelsen / Mads Gravers Jeppesen / Asante Landbrug / Amer Mujezinovic / Bo Hjorth Bentzen / Thomas Nitschke Kledal / Mette Marie Rosenkilde

    Communications Biology, Vol 5, Iss 1, Pp 1-

    How Many SARS-CoV-2 “Viroporins” Are Really Ion Channels?

    2022  Volume 3

    Keywords Biology (General) ; QH301-705.5
    Language English
    Publishing date 2022-08-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Methods for Studying Endocytotic Pathways of Herpesvirus Encoded G Protein-Coupled Receptors

    Maša Mavri / Katja Spiess / Mette Marie Rosenkilde / Catrin Sian Rutland / Milka Vrecl / Valentina Kubale

    Molecules, Vol 25, Iss 5710, p

    2020  Volume 5710

    Abstract: Endocytosis is a fundamental process involved in trafficking of various extracellular and transmembrane molecules from the cell surface to its interior. This enables cells to communicate and respond to external environments, maintain cellular homeostasis, ...

    Abstract Endocytosis is a fundamental process involved in trafficking of various extracellular and transmembrane molecules from the cell surface to its interior. This enables cells to communicate and respond to external environments, maintain cellular homeostasis, and transduce signals. G protein-coupled receptors (GPCRs) constitute a family of receptors with seven transmembrane alpha-helical domains (7TM receptors) expressed at the cell surface, where they regulate physiological and pathological cellular processes. Several herpesviruses encode receptors (vGPCRs) which benefits the virus by avoiding host immune surveillance, supporting viral dissemination, and thereby establishing widespread and lifelong infection, processes where receptor signaling and/or endocytosis seem central. vGPCRs are rising as potential drug targets as exemplified by the cytomegalovirus-encoded receptor US28, where its constitutive internalization has been exploited for selective drug delivery in virus infected cells. Therefore, studying GPCR trafficking is of great importance. This review provides an overview of the current knowledge of endocytic and cell localization properties of vGPCRs and methodological approaches used for studying receptor internalization. Using such novel approaches, we show constitutive internalization of the BILF1 receptor from human and porcine γ-1 herpesviruses and present motifs from the eukaryotic linear motif (ELM) resources with importance for vGPCR endocytosis.
    Keywords endocytosis ; G-protein coupled receptors ; herpesvirus ; methods ; Organic chemistry ; QD241-441
    Subject code 612
    Language English
    Publishing date 2020-12-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Selective Boosting of CCR7-Acting Chemokines; Short Peptides Boost Chemokines with Short Basic Tails, Longer Peptides Boost Chemokines with Long Basic Tails

    Emma Probst Brandum / Astrid Sissel Jørgensen / Marina Barrio Calvo / Katja Spiess / Francis C. Peterson / Zhang Yang / Brian F. Volkman / Christopher T. Veldkamp / Mette Marie Rosenkilde / Christoffer Knak Goth / Gertrud Malene Hjortø

    International Journal of Molecular Sciences, Vol 23, Iss 1397, p

    2022  Volume 1397

    Abstract: The chemokine receptor CCR7 and its ligands CCL19 and CCL21 regulate the lymph node homing of dendritic cells and naïve T-cells and the following induction of a motile DC-T cell priming state. Although CCL19 and CCL21 bind CCR7 with similar affinities, ... ...

    Abstract The chemokine receptor CCR7 and its ligands CCL19 and CCL21 regulate the lymph node homing of dendritic cells and naïve T-cells and the following induction of a motile DC-T cell priming state. Although CCL19 and CCL21 bind CCR7 with similar affinities, CCL21 is a weak agonist compared to CCL19. Using a chimeric chemokine, CCL19 CCL21N-term|C-term , harboring the N-terminus and the C-terminus of CCL21 attached to the core domain of CCL19, we show that these parts of CCL21 act in a synergistic manner to lower ligand potency and determine the way CCL21 engages with CCR7. We have published that a naturally occurring basic C-terminal fragment of CCL21 (C21TP) boosts the signaling of both CCL19 and CCL21. Boosting occurs as a direct consequence of C21TP binding to the CCR7 N-terminus, which seems to free chemokines with basic C-termini from an unfavorable interaction with negatively charged posttranslational modifications in CCR7. Here, we confirm this using a CCL19-variant lacking the basic C-terminus. This variant displays a 22-fold higher potency at CCR7 compared to WT CCL19 and is highly unaffected by the presence of C21TP. WT CCL19 has a short basic C-terminus, CCL21 a longer one. Here, we propose a way to differentially boost CCL19 and CCL21 activity as short and long versions of C21TP boost CCL19 activity, whereas only a long C21TP version can boost chemokines with a full-length CCL21 C-terminus.
    Keywords basic peptide ; CCR7 ; biased signaling ; CCL21 ; CCL19 ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 570
    Language English
    Publishing date 2022-01-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Sustained effect of glucagon on body weight and blood glucose

    Christina Pedersen / Trine Porsgaard / Maria Thomsen / Mette Marie Rosenkilde / Nikolaj Kulahin Roed

    PLoS ONE, Vol 13, Iss 3, p e

    Assessed by continuous glucose monitoring in diabetic rats.

    2018  Volume 0194468

    Abstract: Insulin is a vital part of diabetes treatment, whereas glucagon is primarily used to treat insulin-induced hypoglycemia. However, glucagon is suggested to have a central role in the regulation of body weight, which would be beneficial for diabetic ... ...

    Abstract Insulin is a vital part of diabetes treatment, whereas glucagon is primarily used to treat insulin-induced hypoglycemia. However, glucagon is suggested to have a central role in the regulation of body weight, which would be beneficial for diabetic patients. Since the glucagon effect on blood glucose is known to be transient, it is relevant to investigate the pharmacodynamics of glucagon after repeated dosing. In the present study, we used telemetry to continuously measure blood glucose in streptozotocin induced diabetic Sprague-Dawley rats. This allowed for a more detailed analysis of glucose regulation compared to intermittent blood sampling. In particular, we evaluated the blood glucose-lowering effect of different insulin doses alone, and in combination with a long acting glucagon analog (LAG). We showed how the effect of the LAG accumulated and persisted over time. Furthermore, we found that addition of the LAG decreased body weight without affecting food intake. In a subsequent study, we focused on the glucagon effect on body weight and food intake during equal glycemic control. In order to obtain comparable maximum blood glucose lowering effect to insulin alone, the insulin dose had to be increased four times in combination with 1 nmol/kg of the LAG. In this set-up the LAG prevented further increase in body weight despite the four times higher insulin-dose. However, the body composition was changed. The insulin group increased both lean and fat mass, whereas the group receiving four times insulin in combination with the LAG only significantly increased the fat mass. No differences were observed in food intake, suggesting a direct effect on energy expenditure by glucagon. Surprisingly, we observed decreased levels of FGF21 in plasma compared to insulin treatment alone. With the combination of insulin and the LAG the blood glucose-lowering effect of insulin was prolonged, which could potentially be beneficial in diabetes treatment.
    Keywords Medicine ; R ; Science ; Q
    Subject code 630
    Language English
    Publishing date 2018-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Author Correction

    Trine Lisberg Toft-Bertelsen / Mads Gravers Jeppesen / Eva Tzortzini / Kai Xue / Karin Giller / Stefan Becker / Amer Mujezinovic / Bo Hjorth Bentzen / Loren B. Andreas / Antonios Kolocouris / Thomas Nitschke Kledal / Mette Marie Rosenkilde

    Communications Biology, Vol 4, Iss 1, Pp 1-

    Amantadine inhibits known and novel ion channels encoded by SARS-CoV-2 in vitro

    2021  Volume 2

    Keywords Biology (General) ; QH301-705.5
    Language English
    Publishing date 2021-12-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Amantadine has potential for the treatment of COVID-19 because it inhibits known and novel ion channels encoded by SARS-CoV-2

    Trine Lisberg Toft-Bertelsen / Mads Gravers Jeppesen / Eva Tzortzini / Kai Xue / Karin Giller / Stefan Becker / Amer Mujezinovic / Bo Hjorth Bentzen / Loren B. Andreas / Antonios Kolocouris / Thomas Nitschke Kledal / Mette Marie Rosenkilde

    Communications Biology, Vol 4, Iss 1, Pp 1-

    2021  Volume 10

    Abstract: Toft-Bertelsen et al. describe repurposing of anti-influenza drug amantadine and its derivatives for the treatment of SARS-CoV-2. They show that Amantadine, Emodin and Xanthene show significant blockage of ionchannels formed by SARS-CoV-2 which are ... ...

    Abstract Toft-Bertelsen et al. describe repurposing of anti-influenza drug amantadine and its derivatives for the treatment of SARS-CoV-2. They show that Amantadine, Emodin and Xanthene show significant blockage of ionchannels formed by SARS-CoV-2 which are crucial for its assembly and pathophysiology.
    Keywords Biology (General) ; QH301-705.5
    Language English
    Publishing date 2021-12-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: GPR183 Is Dispensable for B1 Cell Accumulation and Function, but Affects B2 Cell Abundance, in the Omentum and Peritoneal Cavity

    Line Barington / Liv von Voss Christensen / Kristian Kåber Pedersen / Kristine Niss Arfelt / Martin Roumain / Kristian Høj Reveles Jensen / Viktoria Madeline Skovgaard Kjær / Viktorija Daugvilaite / John F. Kearney / Jan Pravsgaard Christensen / Gertrud Malene Hjortø / Giulio G. Muccioli / Peter Johannes Holst / Mette Marie Rosenkilde

    Cells, Vol 11, Iss 494, p

    2022  Volume 494

    Abstract: B1 cells constitute a specialized subset of B cells, best characterized in mice, which is abundant in body cavities, including the peritoneal cavity. Through natural and antigen-induced antibody production, B1 cells participate in the early defense ... ...

    Abstract B1 cells constitute a specialized subset of B cells, best characterized in mice, which is abundant in body cavities, including the peritoneal cavity. Through natural and antigen-induced antibody production, B1 cells participate in the early defense against bacteria. The G protein-coupled receptor 183 (GPR183), also known as Epstein-Barr virus-induced gene 2 (EBI2), is an oxysterol-activated chemotactic receptor that regulates migration of B cells. We investigated the role of GPR183 in B1 cells in the peritoneal cavity and omentum. B1 cells expressed GPR183 at the mRNA level and migrated towards the GPR183 ligand 7α,25-dihydroxycholesterol (7α,25-OHC). GPR183 knock-out (KO) mice had smaller omenta, but with normal numbers of B1 cells, whereas they had fewer B2 cells in the omentum and peritoneal cavity than wildtype (WT) mice. GPR183 was not responsible for B1 cell accumulation in the omentum in response to i.p. lipopolysaccharide (LPS)-injection, in spite of a massive increase in 7α,25-OHC levels. Lack of GPR183 also did not affect B1a- or B1b cell-specific antibody responses after vaccination. In conclusion, we found that GPR183 is non-essential for the accumulation and function of B1 cells in the omentum and peritoneal cavity, but that it influences the abundance of B2 cells in these compartments.
    Keywords GPCR ; 7TM receptor ; GPR183 ; EBI2 ; B1 cell ; B-1 cell ; Biology (General) ; QH301-705.5
    Subject code 570
    Language English
    Publishing date 2022-01-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Structural Diversity in Conserved Regions Like the DRY-Motif among Viral 7TM Receptors—A Consequence of Evolutionary Pressure?

    Ann-Sofie Mølleskov Jensen / Alexander Hovard Sparre-Ulrich / Nicholas Davis-Poynter / Mette Marie Rosenkilde

    Advances in Virology , Vol

    2012  Volume 2012

    Keywords Microbiology ; QR1-502 ; Science ; Q ; DOAJ:Microbiology ; DOAJ:Biology ; DOAJ:Biology and Life Sciences
    Language English
    Publishing date 2012-01-01T00:00:00Z
    Publisher Hindawi Publishing Corporation
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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