Chloroquine inhibits human CD4+ T-cell activation by AP-1 signaling modulation.

Abstract:

:Chloroquine (CQ) is widely used as an anti-inflammatory therapeutic for rheumatic diseases. Although its modes of action on the innate immune system are well described, there is still insufficient knowledge about its direct effects on the adaptive immune system. Thus, we evaluated the influence of CQ on activation parameters of human CD4+ T-cells. CQ directly suppressed proliferation, metabolic activity and cytokine secretion of T-cells following anti-CD3/anti-CD28 activation. In contrast, CQ showed no effect on up-regulation of T-cell activation markers. CQ inhibited activation of all T helper cell subsets, although IL-4 and IL-13 secretion by Th2 cells were less influenced compared to other Th-specific cytokines. Up to 10 μM, CQ did not reduce cell viability, suggesting specific suppressive effects on T-cells. These properties of CQ were fully reversible in re-stimulation experiments. Analyses of intracellular signaling showed that CQ specifically inhibited autophagic flux and additionally activation of AP-1 by reducing phosphorylation of c-JUN. This effect was mediated by inhibition of JNK catalytic activity. In summary, we characterized selective and reversible immunomodulatory effects of CQ on human CD4+ T-cells. These findings provide new insights into the biological actions of JNK/AP-1 signaling in T-cells and may help to expand the therapeutic spectrum of CQ.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Schmidt RL,Jutz S,Goldhahn K,Witzeneder N,Gerner MC,Trapin D,Greiner G,Hoermann G,Steiner G,Pickl WF,Burgmann H,Steinberger P,Ratzinger F,Schmetterer KG

doi

10.1038/srep42191

subject

Has Abstract

pub_date

2017-02-07 00:00:00

pages

42191

issn

2045-2322

pii

srep42191

journal_volume

7

pub_type

杂志文章
  • Characterization of IgG1 Fc Deamidation at Asparagine 325 and Its Impact on Antibody-dependent Cell-mediated Cytotoxicity and FcγRIIIa Binding.

    abstract::Antibody-dependent cell-mediated cytotoxicity (ADCC) is an important mechanism of action for many therapeutic antibodies. A therapeutic immunoglobulin (Ig) G1 monoclonal antibody lost more than half of its ADCC activity after heat stress at 40 °C for 4 months. Size-exclusion and ion-exchange chromatography were used t...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-019-57184-2

    authors: Lu X,Machiesky LA,De Mel N,Du Q,Xu W,Washabaugh M,Jiang XR,Wang J

    更新日期:2020-01-15 00:00:00

  • Pharmacological profile and efficiency in vivo of diflapolin, the first dual inhibitor of 5-lipoxygenase-activating protein and soluble epoxide hydrolase.

    abstract::Arachidonic acid (AA) is metabolized to diverse bioactive lipid mediators. Whereas the 5-lipoxygenase-activating protein (FLAP) facilitates AA conversion by 5-lipoxygenase (5-LOX) to pro-inflammatory leukotrienes (LTs), the soluble epoxide hydrolase (sEH) degrades anti-inflammatory epoxyeicosatrienoic acids (EETs). Ac...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-017-09795-w

    authors: Garscha U,Romp E,Pace S,Rossi A,Temml V,Schuster D,König S,Gerstmeier J,Liening S,Werner M,Atze H,Wittmann S,Weinigel C,Rummler S,Scriba GK,Sautebin L,Werz O

    更新日期:2017-08-24 00:00:00

  • Photochemical analysis of structural transitions in DNA liquid crystals reveals differences in spatial structure of DNA molecules organized in liquid crystalline form.

    abstract::The anisotropic shape of DNA molecules allows them to form lyotropic liquid crystals (LCs) at high concentrations. This liquid crystalline arrangement is also found in vivo (e.g., in bacteriophage capsids, bacteria or human sperm nuclei). However, the role of DNA liquid crystalline organization in living organisms sti...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-018-22863-z

    authors: Brach K,Hatakeyama A,Nogues C,Olesiak-Banska J,Buckle M,Matczyszyn K

    更新日期:2018-03-14 00:00:00

  • A versatile bulk electrotransfection protocol for murine embryonic fibroblasts and iPS cells.

    abstract::Although electroporation has been widely accepted as the main gene transfer tool, there is still considerable scope to improve the electroporation efficiency of exogenous DNAs into primary cells. Here, we developed a square-wave pulsing protocol using OptiMEM-GlutaMAX for highly efficient transfection of murine embryo...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-020-70258-w

    authors: Eghbalsaied S,Hyder I,Kues WA

    更新日期:2020-08-07 00:00:00

  • Circulating microRNAs as potential diagnostic biomarkers for osteoporosis.

    abstract::Osteoporosis is the most common age-related bone disease worldwide and is usually clinically asymptomatic until the first fracture happens. MicroRNAs are critical molecular regulators in bone remodelling processes and are stabilised in the blood. The aim of this project was to identify circulatory microRNAs associated...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-018-26525-y

    authors: Mandourah AY,Ranganath L,Barraclough R,Vinjamuri S,Hof RV,Hamill S,Czanner G,Dera AA,Wang D,Barraclough DL

    更新日期:2018-05-30 00:00:00

  • Coherent Response of Vietnam and Sumatra-Java Upwellings to Cross-Equatorial Winds.

    abstract::Upwelling off Vietnam in the South China Sea (SCS) and the Sumatra-Java upwelling in the Indian Ocean significantly modulate regional variation in climate. Although located in different hemispheres, these upwellings nearly concur during the boreal summer; both are the result of wind-induced Ekman divergence. Beyond se...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-019-40246-w

    authors: Wu CR,Wang LC,Wang YL,Lin YF,Chiang TL,Hsin YC

    更新日期:2019-03-06 00:00:00

  • A novel Mitosomal β-barrel Outer Membrane Protein in Entamoeba.

    abstract::Entamoeba possesses a highly divergent mitochondrion-related organelle known as the mitosome. Here, we report the discovery of a novel protein in Entamoeba, which we name Mitosomal β-barrel Outer Membrane Protein of 30 kDa (MBOMP30). Initially identified through in silico analysis, we experimentally confirmed that MBO...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/srep08545

    authors: Santos HJ,Imai K,Makiuchi T,Tomii K,Horton P,Nozawa A,Ibrahim M,Tozawa Y,Nozaki T

    更新日期:2015-02-25 00:00:00

  • Publisher Correction: Association between self-reported physical activity and incident atrial fibrillation in a young Korean population.

    abstract::A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper. ...

    journal_title:Scientific reports

    pub_type: 已发布勘误

    doi:10.1038/s41598-019-44437-3

    authors: Lee SH,Ryu S,Lee JY,Seo DC,Kim BJ,Sung KC

    更新日期:2019-06-05 00:00:00

  • Reference Genes for Expression Studies in Human CD8+ Naïve and Effector Memory T Cells under Resting and Activating Conditions.

    abstract::Reverse-transcription quantitative real-time polymerase chain reaction (RT-qPCR) is widely used for mRNA quantification. To accurately measure changing gene transcript levels under different experimental conditions, the use of appropriate reference gene transcripts is instrumental. In T cell immunology, suitable refer...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-020-66367-1

    authors: Geigges M,Gubser PM,Unterstab G,Lecoultre Y,Paro R,Hess C

    更新日期:2020-06-10 00:00:00

  • Altering Compliance of a Load Carriage Device in the Medial-Lateral Direction Reduces Peak Forces While Walking.

    abstract::Altering mechanical compliance in load carriage structures has shown to reduce metabolic cost and accelerative forces of carrying weight. Currently, modifications to load carriage structures have been primarily targeted at vertical motion of the carried mass. No study to date has investigated altering load carriage co...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-018-32175-x

    authors: Martin JP,Li Q

    更新日期:2018-09-13 00:00:00

  • Enhanced electrocatalytic performance for oxygen reduction via active interfaces of layer-by-layered titanium nitride/titanium carbonitride structures.

    abstract::Cathode materials always limit the performance of fuel cells while the commercial platinum-based catalysts hardly meet the requirements of low cost, durable and stable. Here a non-precious metal oxygen reduction reaction (ORR) electocatalyst based on titanium nitride/titanium carbonitride hierarchical structures (TNTC...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/srep06712

    authors: Jin Z,Li P,Xiao D

    更新日期:2014-10-22 00:00:00

  • Histone Variant MacroH2A1 Plays an Isoform-Specific Role in Suppressing Epithelial-Mesenchymal Transition.

    abstract::Epithelial-Mesenchymal Transition (EMT) is a biological program that plays key roles in various developmental and pathological processes. Although much work has been done on signaling pathways and transcription factors regulating EMT, the epigenetic regulation of EMT remains not well understood. Histone variants have ...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-018-19364-4

    authors: Hodge DQ,Cui J,Gamble MJ,Guo W

    更新日期:2018-01-16 00:00:00

  • Evaluation of left ventricular strain in patients with arrhythmia based on the 3T MR temporal parallel acquisition technique.

    abstract::Most of the current studies on myocardial strain are mainly applied in patients with sinus rhythm because the image quality of arrhythmias obtained with conventional scanning sequences does not meet diagnostic needs. Here, we intend to assess left ventricular (LV) global myocardial strain in patients with arrhythmias ...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-020-66315-z

    authors: Chen H,Xie RM,Zhao L,Zhang XY,Zhao YK,Wang Z,Xie GX,Ma XH

    更新日期:2020-06-09 00:00:00

  • First Detection of DS-1-like G1P[8] Double-gene Reassortant Rotavirus Strains on The American Continent, Brazil, 2013.

    abstract::Emergence of DS-1-like-G1P[8] rotavirus in Asia have been recently reported. We report for the first time the detection and the whole genome phylogenetic analysis of DS-1-like-G1P[8] strains in America. From 2013 to 2017, a total of 4226 fecal samples were screened for rotavirus by ELISA, PAGE, RT-PCR and sequencing. ...

    journal_title:Scientific reports

    pub_type: 历史文章,杂志文章

    doi:10.1038/s41598-019-38703-7

    authors: Luchs A,da Costa AC,Cilli A,Komninakis SCV,Carmona RCC,Morillo SG,Sabino EC,Timenetsky MDCST

    更新日期:2019-02-18 00:00:00

  • Efficacy and safety of GLP-1 receptor agonists as add-on to SGLT2 inhibitors in type 2 diabetes mellitus: A meta-analysis.

    abstract::GLP-1 receptor agonists (GLP-1RA) and SGLT2 inhibitors (SGLT2i) have been associated with improved glycemic control, body weight loss and favorable changes in cardiovascular risk factors and outcomes. We conducted a systematic review and meta-analysis to evaluate the effects of the addition of GLP-1RA to SGLT2i in pat...

    journal_title:Scientific reports

    pub_type: 杂志文章,meta分析

    doi:10.1038/s41598-019-55524-w

    authors: Castellana M,Cignarelli A,Brescia F,Perrini S,Natalicchio A,Laviola L,Giorgino F

    更新日期:2019-12-18 00:00:00

  • Polarization in social media assists influencers to become more influential: analysis and two inoculation strategies.

    abstract::This work explores simulations of polarized discussions from a general and theoretical premise. Specifically the question of whether a plausible avenue exists for a subgroup in an online social network to find a disagreement beneficial and what that benefit could be. A methodological framework is proposed which repres...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-019-55178-8

    authors: Garibay I,Mantzaris AV,Rajabi A,Taylor CE

    更新日期:2019-12-09 00:00:00

  • Design principles governing chemomechanical coupling of kinesin.

    abstract::A systematic chemomechanical network model for the molecular motor kinesin is presented in this report. The network model is based on the nucleotide-dependent binding affinity of the heads to an microtubule (MT) and the asymmetries and similarities between the chemical transitions caused by the intramolecular strain b...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-017-01328-9

    authors: Sumi T

    更新日期:2017-04-25 00:00:00

  • Identification of novel molecular signatures of IgA nephropathy through an integrative -omics analysis.

    abstract::IgA nephropathy (IgAN) is the most prevalent among primary glomerular diseases worldwide. Although our understanding of IgAN has advanced significantly, its underlying biology and potential drug targets are still unexplored. We investigated a combinatorial approach for the analysis of IgAN-relevant -omics data, aiming...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-017-09393-w

    authors: Krochmal M,Cisek K,Filip S,Markoska K,Orange C,Zoidakis J,Gakiopoulou C,Spasovski G,Mischak H,Delles C,Vlahou A,Jankowski J

    更新日期:2017-08-22 00:00:00

  • The EphB6 receptor is overexpressed in pediatric T cell acute lymphoblastic leukemia and increases its sensitivity to doxorubicin treatment.

    abstract::While impressive improvements have been achieved in T-ALL therapy, current treatment approaches fail in approximately 25% of patients and these patients have limited treatment options. Another significant group of patients is being overtreated, which causes long-lasting side effects. Identification of molecules contro...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-017-15200-3

    authors: El Zawily A,McEwen E,Toosi B,Vizeacoumar FS,Freywald T,Vizeacoumar FJ,Freywald A

    更新日期:2017-11-07 00:00:00

  • Dimerisation induced formation of the active site and the identification of three metal sites in EAL-phosphodiesterases.

    abstract::The bacterial second messenger cyclic di-3',5'-guanosine monophosphate (c-di-GMP) is a key regulator of bacterial motility and virulence. As high levels of c-di-GMP are associated with the biofilm lifestyle, c-di-GMP hydrolysing phosphodiesterases (PDEs) have been identified as key targets to aid development of novel ...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/srep42166

    authors: Bellini D,Horrell S,Hutchin A,Phippen CW,Strange RW,Cai Y,Wagner A,Webb JS,Tews I,Walsh MA

    更新日期:2017-02-10 00:00:00

  • The Role of a Crystallographically Unresolved Cytoplasmic Loop in Stabilizing the Bacterial Membrane Insertase YidC2.

    abstract::YidC, a bacterial member of the YidC/Alb3/Oxa1 insertase family, mediates membrane protein assembly and insertion. Cytoplasmic loops are known to have functional significance in membrane proteins such as YidC. Employing microsecond-level molecular dynamics (MD) simulations, we show that the crystallographically unreso...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-019-51052-9

    authors: Harkey T,Govind Kumar V,Hettige J,Tabari SH,Immadisetty K,Moradi M

    更新日期:2019-10-08 00:00:00

  • Solar thermal polymerase chain reaction for smartphone-assisted molecular diagnostics.

    abstract::Nucleic acid-based diagnostic techniques such as polymerase chain reaction (PCR) are used extensively in medical diagnostics due to their high sensitivity, specificity and quantification capability. In settings with limited infrastructure and unreliable electricity, however, access to such devices is often limited due...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/srep04137

    authors: Jiang L,Mancuso M,Lu Z,Akar G,Cesarman E,Erickson D

    更新日期:2014-02-20 00:00:00

  • Reconstruction of noise-driven nonlinear networks from node outputs by using high-order correlations.

    abstract::Many practical systems can be described by dynamic networks, for which modern technique can measure their outputs, and accumulate extremely rich data. Nevertheless, the network structures producing these data are often deeply hidden in the data. The problem of inferring network structures by analyzing the available da...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/srep44639

    authors: Chen Y,Zhang Z,Chen T,Wang S,Hu G

    更新日期:2017-03-21 00:00:00

  • A Novel PET Imaging Probe for the Detection and Monitoring of Translocator Protein 18 kDa Expression in Pathological Disorders.

    abstract::A new fluorine-substituted ligand, compound 1 (CB251), with a very high affinity (Ki = 0.27 ± 0.09 nM) and selectivity for the 18-kDa translocator protein (TSPO), is presented as an attractive biomarker for the diagnosis of neuroinflammation, neurodegeneration and tumour progression. To test compound 1 as a TSPO PET i...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/srep20422

    authors: Perrone M,Moon BS,Park HS,Laquintana V,Jung JH,Cutrignelli A,Lopedota A,Franco M,Kim SE,Lee BC,Denora N

    更新日期:2016-02-08 00:00:00

  • CRISRP/Cas9-mediated knockout of Mct8 reveals a functional involvement of Mct8 in testis and sperm development in a rat.

    abstract::Thyroid hormone (TH) has long been believed to play a minor role in male reproduction. However, evidences from experimental model of thyrotoxicosis or hypothyroidism suggests its role in spermatogenesis. Cellular action of TH requires membrane transport via specific transporters such as monocarboxylate transporter 8 (...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-020-67594-2

    authors: Bae HS,Jin YK,Ham S,Kim HK,Shin H,Cho GB,Lee KJ,Lee H,Kim KM,Koo OJ,Jang G,Lee JM,Lee JY

    更新日期:2020-07-07 00:00:00

  • Multiplexed Spliced-Leader Sequencing: A high-throughput, selective method for RNA-seq in Trypanosomatids.

    abstract::High throughput sequencing techniques are poorly adapted for in vivo studies of parasites, which require prior in vitro culturing and purification. Trypanosomatids, a group of kinetoplastid protozoans, possess a distinctive feature in their transcriptional mechanism whereby a specific Spliced Leader (SL) sequence is a...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-017-03987-0

    authors: Cuypers B,Domagalska MA,Meysman P,Muylder G,Vanaerschot M,Imamura H,Dumetz F,Verdonckt TW,Myler PJ,Ramasamy G,Laukens K,Dujardin JC

    更新日期:2017-06-16 00:00:00

  • Leptin Promotes Allergic Airway Inflammation through Targeting the Unfolded Protein Response Pathway.

    abstract::Allergic asthma and obesity are major public health problems in the world. Recent Meta-analysis studies implicated a positive relationship between serum leptin, which is elevated in obese individuals, and the risk of asthma. However, it is not well understood how obesity-associated elevation of leptin increases the ri...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-018-27278-4

    authors: Zheng H,Wu D,Wu X,Zhang X,Zhou Q,Luo Y,Yang X,Chock CJ,Liu M,Yang XO

    更新日期:2018-06-11 00:00:00

  • Modular type I polyketide synthase acyl carrier protein domains share a common N-terminally extended fold.

    abstract::Acyl carrier protein (ACP) domains act as interaction hubs within modular polyketide synthase (PKS) systems, employing specific protein-protein interactions to present acyl substrates to a series of enzyme active sites. Many domains from the multimodular PKS that generates the toxin mycolactone display an unusually hi...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-019-38747-9

    authors: Moretto L,Heylen R,Holroyd N,Vance S,Broadhurst RW

    更新日期:2019-02-20 00:00:00

  • Bursaphelenchus xylophilus is killed by homologues of 2-(1-undecyloxy)-1-ethanol.

    abstract::2-(1-Undecyloxy)-1-ethanol, monochamol, is a male-produced aggregation pheromone of the Monochamus species, which are efficient vectors of the pine wood nematode (PWN), Bursaphelenchus xylophilus, which cause devastating damage to pines worldwide. The nematicidal activity of synthetic monochamol and its homologues (RO...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/srep29300

    authors: Kim J,Lee SM,Park CG

    更新日期:2016-07-11 00:00:00

  • Vasohibin-1 rescues erectile function through up-regulation of angiogenic factors in the diabetic mice.

    abstract::Neovascularization of the erectile tissue emerges as a beneficial curative approach to treat erectile dysfunction (ED). Here we for the first time report the unexpected role of vasohibin-1 (VASH1), mainly known as an anti-angiogenic factor, in restoring erectile function in diabetic mice. A diabetic patient has lower ...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-020-80925-7

    authors: Song KM,Kim WJ,Choi MJ,Kwon KD,Limanjaya A,Ghatak K,Ock J,Yin GN,Sato Y,Hong SS,Ryu JK,Suh JK

    更新日期:2021-01-13 00:00:00