当前位置： SCI文献检索 > Science Signaling期刊下所有文献 > Quantitative analysis of competitive cytokine signaling predicts tissue thresholds for the propagation of macrophage activation.

Quantitative analysis of competitive cytokine signaling predicts tissue thresholds for the propagation of macrophage activation.

Abstract：

:Toll-like receptor (TLR) signaling regulates macrophage activation and effector cytokine propagation in the constrained environment of a tissue. In macrophage populations, TLR4 stimulates the dose-dependent transcription of nuclear factor κB (NF-κB) target genes. However, using single-RNA counting, we found that individual cells exhibited a wide range (three orders of magnitude) of expression of the gene encoding the proinflammatory cytokine tumor necrosis factor-α (TNF-α). The TLR4-induced TNFA transcriptional response correlated with the extent of NF-κB signaling in the cells and their size. We compared the rates of TNF-α production and uptake in macrophages and mouse embryonic fibroblasts and generated a mathematical model to explore the heterogeneity in the response of macrophages to TLR4 stimulation and the propagation of the TNF-α signal in the tissue. The model predicts that the local propagation of the TLR4-dependent TNF-α response and cellular NF-κB signaling are limited to small distances of a few cell diameters between neighboring tissue-resident macrophages. In our predictive model, TNF-α propagation was constrained by competitive uptake of TNF-α from the environment, rather than by heterogeneous production of the cytokine. We propose that the highly constrained architecture of tissues enables effective localized propagation of inflammatory cues while avoiding out-of-context responses at longer distances.

journal_name

Sci Signal

journal_title

Science signaling

authors

Bagnall J,Boddington C,England H,Brignall R,Downton P,Alsoufi Z,Boyd J,Rowe W,Bennett A,Walker C,Adamson A,Patel NMX,O'Cualain R,Schmidt L,Spiller DG,Jackson DA,Müller W,Muldoon M,White MRH,Paszek P

doi

10.1126/scisignal.aaf3998

subject

Has Abstract

pub_date

2018-07-24 00:00:00

issue

540

eissn

1945-0877

issn

1937-9145

pii

11/540/eaaf3998

journal_volume

11

pub_type

杂志文章

相关文献

Science Signaling文献大全
  • Regulation of the 26S proteasome complex during oxidative stress.

    abstract：:The proteasome plays a pivotal role in the cellular response to oxidative stress. Here, we used biochemical and mass spectrometric methods to investigate structural changes in the 26S proteasomes from yeast and mammalian cells exposed to hydrogen peroxide (H₂O₂). Oxidative stress induced the dissociation of the 20S co...

    journal_title：Science signaling

    pub_type： 杂志文章

    doi：10.1126/scisignal.2001232

    authors： Wang X,Yen J,Kaiser P,Huang L

    更新日期：2010-12-07 00:00:00

  • The E3 ligase RNF43 inhibits Wnt signaling downstream of mutated β-catenin by sequestering TCF4 to the nuclear membrane.

    abstract：:Given its fundamental role in development and cancer, the Wnt-β-catenin signaling pathway is tightly controlled at multiple levels. RING finger protein 43 (RNF43) is an E3 ubiquitin ligase originally found in stem cells and proposed to inhibit Wnt signaling by interacting with the Wnt receptors of the Frizzled family....

    journal_title：Science signaling

    pub_type： 杂志文章

    doi：10.1126/scisignal.aac6757

    authors： Loregger A,Grandl M,Mejías-Luque R,Allgäuer M,Degenhart K,Haselmann V,Oikonomou C,Hatzis P,Janssen KP,Nitsche U,Gradl D,van den Broek O,Destree O,Ulm K,Neumaier M,Kalali B,Jung A,Varela I,Schmid RM,Rad R,Busch DH

    更新日期：2015-09-08 00:00:00

  • Parasitic worms stimulate host NADPH oxidases to produce reactive oxygen species that limit plant cell death and promote infection.

    abstract：:Plants and animals produce reactive oxygen species (ROS) in response to infection. In plants, ROS not only activate defense responses and promote cell death to limit the spread of pathogens but also restrict the amount of cell death in response to pathogen recognition. Plants also use hormones, such as salicylic acid,...

    journal_title：Science signaling

    pub_type： 杂志文章

    doi：10.1126/scisignal.2004777

    authors： Siddique S,Matera C,Radakovic ZS,Hasan MS,Gutbrod P,Rozanska E,Sobczak M,Torres MA,Grundler FM

    更新日期：2014-04-08 00:00:00

  • Acetylation goes global: the emergence of acetylation biology.

    abstract：:For the first 30 years since its discovery, reversible protein acetylation has been studied and understood almost exclusively in the context of histone modification and gene transcription. With the discovery of non-histone acetylated proteins and acetylation-modifying enzymes in cellular compartments outside the nucle...

    journal_title：Science signaling

    pub_type： 杂志文章

    doi：10.1126/scisignal.297pe76

    authors： Norris KL,Lee JY,Yao TP

    更新日期：2009-11-17 00:00:00

  • Parkin mediates mitophagy during beige-to-white fat conversion.

    abstract：:In this issue of Science Signaling, Lu et al reveal a role for Parkin-mediated mitophagy in beige-to-white adipocyte transition. In the absence of Parkin, mitochondria in thermogenic beige adipocytes are preserved even after the elimination of cold mimetic stimuli-in contrast to their typical elimination during the wh...

    journal_title：Science signaling

    pub_type： 评论,杂志文章,评审

    doi：10.1126/scisignal.aat1082

    authors： Sarraf SA,Youle RJ

    更新日期：2018-04-24 00:00:00

  • Educated natural killer cells show dynamic movement of the activating receptor NKp46 and confinement of the inhibitory receptor Ly49A.

    abstract：:Educated natural killer (NK) cells have inhibitory receptors specific for self major histocompatibility complex (MHC) class I molecules and kill cancer cells more efficiently than do NK cells that do not have such receptors (hyporesponsive NK cells). The mechanism behind this functional empowerment through education h...

    journal_title：Science signaling

    pub_type： 杂志文章

    doi：10.1126/scisignal.aai9200

    authors： Staaf E,Hedde PN,Bagawath Singh S,Piguet J,Gratton E,Johansson S

    更新日期：2018-02-13 00:00:00

  • STIM2 enhances receptor-stimulated Ca²⁺ signaling by promoting recruitment of STIM1 to the endoplasmic reticulum-plasma membrane junctions.

    abstract：:A central component of receptor-evoked Ca(2+) signaling is store-operated Ca(2+) entry (SOCE), which is activated by the assembly of STIM1-Orai1 channels in endoplasmic reticulum (ER) and plasma membrane (PM) (ER-PM) junctions in response to depletion of ER Ca(2+). We report that STIM2 enhances agonist-mediated activa...

    journal_title：Science signaling

    pub_type： 杂志文章

    doi：10.1126/scisignal.2005748

    authors： Ong HL,de Souza LB,Zheng C,Cheng KT,Liu X,Goldsmith CM,Feske S,Ambudkar IS

    更新日期：2015-01-13 00:00:00

  • Focus issue: uncovering the mechanisms of neurological disease.

    abstract：:This week, Science Signaling highlights research that uses computational and cell biology approaches to uncover the molecular mechanisms underlying diseases of the central nervous system. In particular, research featured explores the neuronal response to stress due to excess excitatory stimuli, multiple roles for pres...

    journal_title：Science signaling

    pub_type： 杂志文章,评审

    doi：10.1126/scisignal.2004456

    authors： Ferrarelli LK,Gough NR

    更新日期：2013-07-09 00:00:00

  • MARK3-mediated phosphorylation of ARHGEF2 couples microtubules to the actin cytoskeleton to establish cell polarity.

    abstract：:The PAR-1-MARK pathway controls cell polarity through the phosphorylation of microtubule-associated proteins. Rho-Rac guanine nucleotide exchange factor 2 (ARHGEF2), which activates Ras homolog family member A (RHOA), is anchored to the microtubule network and sequestered in an inhibited state through binding to dynei...

    journal_title：Science signaling

    pub_type： 杂志文章

    doi：10.1126/scisignal.aan3286

    authors： Sandí MJ,Marshall CB,Balan M,Coyaud É,Zhou M,Monson DM,Ishiyama N,Chandrakumar AA,La Rose J,Couzens AL,Gingras AC,Raught B,Xu W,Ikura M,Morrison DK,Rottapel R

    更新日期：2017-10-31 00:00:00

  • Receptor cooperation in B cells.

    abstract：:TLR4-stimulated B cell activation is mediated by the tyrosine kinase Syk and depends on the B cell receptor. ...

    journal_title：Science signaling

    pub_type： 评论,杂志文章

    doi：10.1126/scisignal.aan7951

    authors： Foley JF

    更新日期：2017-05-23 00:00:00

  • Aβ oligomers induce pathophysiological mGluR5 signaling in Alzheimer's disease model mice in a sex-selective manner.

    abstract：:The prevalence, presentation, and progression of Alzheimer's disease (AD) differ between men and women, although β-amyloid (Aβ) deposition is a pathological hallmark of AD in both sexes. Aβ-induced activation of the neuronal glutamate receptor mGluR5 is linked to AD progression. However, we found that mGluR5 exhibits ...

    journal_title：Science signaling

    pub_type： 杂志文章

    doi：10.1126/scisignal.abd2494

    authors： Abd-Elrahman KS,Albaker A,de Souza JM,Ribeiro FM,Schlossmacher MG,Tiberi M,Hamilton A,Ferguson SSG

    更新日期：2020-12-15 00:00:00

  • Novel p47(phox)-related organizers regulate localized NADPH oxidase 1 (Nox1) activity.

    abstract：:The mechanisms that determine localized formation of reactive oxygen species (ROS) through NADPH (reduced form of nicotinamide adenine dinucleotide phosphate) oxidase (Nox) family members in nonphagocytic cells are unknown. We show that the c-Src substrate proteins Tks4 (tyrosine kinase substrate with four SH3 domains...

    journal_title：Science signaling

    pub_type： 杂志文章

    doi：10.1126/scisignal.2000370

    authors： Gianni D,Diaz B,Taulet N,Fowler B,Courtneidge SA,Bokoch GM

    更新日期：2009-09-15 00:00:00

  • Subtle modifications to oxytocin produce ligands that retain potency and improved selectivity across species.

    abstract：:Oxytocin and vasopressin mediate various physiological functions that are important for osmoregulation, reproduction, cardiovascular function, social behavior, memory, and learning through four G protein-coupled receptors that are also implicated in high-profile disorders. Targeting these receptors is challenging beca...

    journal_title：Science signaling

    pub_type： 杂志文章

    doi：10.1126/scisignal.aan3398

    authors： Muttenthaler M,Andersson Å,Vetter I,Menon R,Busnelli M,Ragnarsson L,Bergmayr C,Arrowsmith S,Deuis JR,Chiu HS,Palpant NJ,O'Brien M,Smith TJ,Wray S,Neumann ID,Gruber CW,Lewis RJ,Alewood PF

    更新日期：2017-12-05 00:00:00

  • CCR5 adopts three homodimeric conformations that control cell surface delivery.

    abstract：:Biophysical methods and x-ray crystallography have revealed that class A G protein-coupled receptors (GPCRs) can form homodimers. We combined computational approaches with receptor cross-linking, energy transfer, and a newly developed functional export assay to characterize the residues involved in the dimerization in...

    journal_title：Science signaling

    pub_type： 杂志文章

    doi：10.1126/scisignal.aal2869

    authors： Jin J,Momboisse F,Boncompain G,Koensgen F,Zhou Z,Cordeiro N,Arenzana-Seisdedos F,Perez F,Lagane B,Kellenberger E,Brelot A

    更新日期：2018-05-08 00:00:00

  • The adaptor protein insulin receptor substrate 2 inhibits alternative macrophage activation and allergic lung inflammation.

    abstract：:Insulin receptor substrate 2 (IRS2) is an adaptor protein that becomes tyrosine-phosphorylated in response to the cytokines interleukin-4 (IL-4) and IL-13, which results in activation of the phosphoinositide 3-kinase (PI3K)-Akt pathway. IL-4 and IL-13 contribute to allergic lung inflammation. To examine the role of IR...

    journal_title：Science signaling

    pub_type： 杂志文章

    doi：10.1126/scisignal.aad6724

    authors： Dasgupta P,Dorsey NJ,Li J,Qi X,Smith EP,Yamaji-Kegan K,Keegan AD

    更新日期：2016-06-21 00:00:00

  • Hypusine biosynthesis in β cells links polyamine metabolism to facultative cellular proliferation to maintain glucose homeostasis.

    abstract：:Deoxyhypusine synthase (DHPS) uses the polyamine spermidine to catalyze the hypusine modification of the mRNA translation factor eIF5A and promotes oncogenesis through poorly defined mechanisms. Because germline deletion of Dhps is embryonically lethal, its role in normal postnatal cellular function in vivo remains un...

    journal_title：Science signaling

    pub_type： 杂志文章

    doi：10.1126/scisignal.aax0715

    authors： Levasseur EM,Yamada K,Piñeros AR,Wu W,Syed F,Orr KS,Anderson-Baucum E,Mastracci TL,Maier B,Mosley AL,Liu Y,Bernal-Mizrachi E,Alonso LC,Scott D,Garcia-Ocaña A,Tersey SA,Mirmira RG

    更新日期：2019-12-03 00:00:00

  • The adhesion GPCR BAI1 mediates macrophage ROS production and microbicidal activity against Gram-negative bacteria.

    abstract：:The detection of microbes and initiation of an innate immune response occur through pattern recognition receptors (PRRs), which are critical for the production of inflammatory cytokines and activation of the cellular microbicidal machinery. In particular, the production of reactive oxygen species (ROS) by the NADPH ox...

    journal_title：Science signaling

    pub_type： 杂志文章

    doi：10.1126/scisignal.aac6250

    authors： Billings EA,Lee CS,Owen KA,D'Souza RS,Ravichandran KS,Casanova JE

    更新日期：2016-02-02 00:00:00

  • Direct binding between Orai1 and AC8 mediates dynamic interplay between Ca2+ and cAMP signaling.

    abstract：:The interplay between calcium ion (Ca(2+)) and cyclic adenosine monophosphate (cAMP) signaling underlies crucial aspects of cell homeostasis. The membrane-bound Ca(2+)-regulated adenylyl cyclases (ACs) are pivotal points of this integration. These enzymes display high selectivity for Ca(2+) entry arising from the acti...

    journal_title：Science signaling

    pub_type： 杂志文章

    doi：10.1126/scisignal.2002299

    authors： Willoughby D,Everett KL,Halls ML,Pacheco J,Skroblin P,Vaca L,Klussmann E,Cooper DM

    更新日期：2012-04-10 00:00:00

  • IRE1α prevents hepatic steatosis by processing and promoting the degradation of select microRNAs.

    abstract：:Obesity or a high-fat diet represses the endoribonuclease activity of inositol-requiring enzyme 1α (IRE1α), a transducer of the unfolded protein response (UPR) in cells under endoplasmic reticulum (ER) stress. An impaired UPR is associated with hepatic steatosis and nonalcoholic fatty liver disease (NAFLD), which is c...

    journal_title：Science signaling

    pub_type： 杂志文章

    doi：10.1126/scisignal.aao4617

    authors： Wang JM,Qiu Y,Yang Z,Kim H,Qian Q,Sun Q,Zhang C,Yin L,Fang D,Back SH,Kaufman RJ,Yang L,Zhang K

    更新日期：2018-05-15 00:00:00

  • Convergence of Wnt, growth factor, and heterotrimeric G protein signals on the guanine nucleotide exchange factor Daple.

    abstract：:Cellular proliferation, differentiation, and morphogenesis are shaped by multiple signaling cascades, and their dysregulation plays an integral role in cancer progression. Three cascades that contribute to oncogenic potential are those mediated by Wnt proteins and the receptor Frizzled (FZD), growth factor receptor ty...

    journal_title：Science signaling

    pub_type： 杂志文章

    doi：10.1126/scisignal.aao4220

    authors： Aznar N,Ear J,Dunkel Y,Sun N,Satterfield K,He F,Kalogriopoulos NA,Lopez-Sanchez I,Ghassemian M,Sahoo D,Kufareva I,Ghosh P

    更新日期：2018-02-27 00:00:00

  • Extensive crosstalk between O-GlcNAcylation and phosphorylation regulates cytokinesis.

    abstract：:Like phosphorylation, the addition of O-linked beta-N-acetylglucosamine (O-GlcNAcylation) is a ubiquitous, reversible process that modifies serine and threonine residues on nuclear and cytoplasmic proteins. Overexpression of the enzyme that adds O-GlcNAc to target proteins, O-GlcNAc transferase (OGT), perturbs cytokin...

    journal_title：Science signaling

    pub_type： 杂志文章

    doi：10.1126/scisignal.2000526

    authors： Wang Z,Udeshi ND,Slawson C,Compton PD,Sakabe K,Cheung WD,Shabanowitz J,Hunt DF,Hart GW

    更新日期：2010-01-12 00:00:00

  • 2009: signaling breakthroughs of the year.

    abstract：:Nominations for this year's signaling breakthroughs spanned physiology, therapeutics and drug development, neuroscience, and plant signaling. Among the most exciting advances in mammalian biology were therapeutic applications of research that are overturning the conventional boundaries of signaling pathways,unexpected...

    journal_title：Science signaling

    pub_type： 社论,历史文章,评审

    doi：10.1126/scisignal.3103eg1

    authors： Adler EM

    更新日期：2010-01-05 00:00:00

  • ER stress in pancreatic beta cells: the thin red line between adaptation and failure.

    abstract：:Secretory cells, such as pancreatic beta cells, face the challenge of increasing protein synthesis severalfold during acute or chronic stimulation. This poses a burden on the endoplasmic reticulum (ER), the organelle where proinsulin synthesis and folding takes place. Thus, beta cells use various adaptive mechanisms t...

    journal_title：Science signaling

    pub_type： 杂志文章,评审

    doi：10.1126/scisignal.3110pe7

    authors： Eizirik DL,Cnop M

    更新日期：2010-02-23 00:00:00

  • How Ca2+-permeable AMPA receptors, the kinase PKA, and the phosphatase PP2B are intertwined in synaptic LTP and LTD.

    abstract：:Both synaptic long-term potentiation (LTP) and long-term depression (LTD) are thought to be critical for memory formation. Dell'Acqua and co-workers now demonstrate that transient postsynaptic incorporation of Ca(2+)-permeable (CP) α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) is required for...

    journal_title：Science signaling

    pub_type： 杂志文章,评审

    doi：10.1126/scisignal.aaf7067

    authors： Hell JW

    更新日期：2016-04-26 00:00:00

  • Beta-adrenergic regulation of the L-type Ca2+ channel Ca(V)1.2 by PKA rekindles excitement.

    abstract：:When we are frightened, our hearts beat more rapidly and forcefully so we can fight more intensely or run away faster. This fight-or-flight response is triggered by the release of norepinephrine from neurons of the sympathetic nervous system. Norepinephrine activates the classic β-adrenergic receptor-heterotrimeric G(...

    journal_title：Science signaling

    pub_type： 评论,杂志文章

    doi：10.1126/scisignal.3141pe33

    authors： Hell JW

    更新日期：2010-09-28 00:00:00

  • The early synthesis of p35 and activation of CDK5 in LPS-stimulated macrophages suppresses interleukin-10 production.

    abstract：:Interleukin-10 (IL-10) is an important anti-inflammatory cytokine that is produced primarily by macrophages. We investigated mechanisms by which the timing of IL-10 production was controlled in macrophages and found that cyclin-dependent kinase 5 (CDK5) activity was markedly increased in lipopolysaccharide (LPS)-stimu...

    journal_title：Science signaling

    pub_type： 杂志文章

    doi：10.1126/scisignal.aab3156

    authors： Na YR,Jung D,Gu GJ,Jang AR,Suh YH,Seok SH

    更新日期：2015-11-24 00:00:00

  • Acetylation of Ets-1 is the key to chromatin remodeling for miR-192 expression.

    abstract：:By regulating gene expression, microRNAs (miRNAs) play pivotal roles in physiological and pathological processes. However, the regulation of miRNAs is elusive. miR-192 is a key regulator of renal fibrosis and hypertrophy in diabetic nephropathy. Natarajan et al. showed that the miR-192 gene contains an upstream region...

    journal_title：Science signaling

    pub_type： 杂志文章

    doi：10.1126/scisignal.2004299

    authors： Dong Z

    更新日期：2013-06-04 00:00:00

  • Neratinib is effective in breast tumors bearing both amplification and mutation of ERBB2 (HER2).

    abstract：:Mutations in ERBB2, the gene encoding epidermal growth factor receptor (EGFR) family member HER2, are common in and drive the growth of "HER2-negative" (not ERBB2 amplified) tumors but are rare in "HER2-positive" (ERBB2 amplified) breast cancer. We analyzed DNA-sequencing data from HER2-positive patients and used cell...

    journal_title：Science signaling

    pub_type： 杂志文章

    doi：10.1126/scisignal.aat9773

    authors： Cocco E,Javier Carmona F,Razavi P,Won HH,Cai Y,Rossi V,Chan C,Cownie J,Soong J,Toska E,Shifman SG,Sarotto I,Savas P,Wick MJ,Papadopoulos KP,Moriarty A,Cutler RE Jr,Avogadri-Connors F,Lalani AS,Bryce RP,Chandarlapa

    更新日期：2018-10-09 00:00:00

  • Lgl reduces endosomal vesicle acidification and Notch signaling by promoting the interaction between Vap33 and the V-ATPase complex.

    abstract：:Epithelial cell polarity is linked to the control of tissue growth and tumorigenesis. The tumor suppressor and cell polarity protein lethal-2-giant larvae (Lgl) promotes Hippo signaling and inhibits Notch signaling to restrict tissue growth in Drosophila melanogaster Notch signaling is greater in lgl mutant tissue tha...

    journal_title：Science signaling

    pub_type： 杂志文章

    doi：10.1126/scisignal.aar1976

    authors： Portela M,Yang L,Paul S,Li X,Veraksa A,Parsons LM,Richardson HE

    更新日期：2018-06-05 00:00:00

  • Costimulatory role of CXCR4 with pre-TCR and its crosstalk with PI3K in beta-selection of thymocytes.

    abstract：:Chemokines were initially thought of only as regulators of the migration of developing thymocytes between different compartments of the thymus and were predicted also to be involved in early stages of thymocyte development. Recent data have suggested additional functions for the chemokine receptor CXCR4-a G protein-co...

    journal_title：Science signaling

    pub_type： 杂志文章

    doi：10.1126/scisignal.3119jc4

    authors： Ahamed JA,Madhivadhani P

    更新日期：2010-04-27 00:00:00