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  1. Article ; Online: Multi-scale in vivo systems analysis reveals the influence of immune cells on TNF-α-induced apoptosis in the intestinal epithelium.

    Ken S Lau / Virna Cortez-Retamozo / Sarah R Philips / Mikael J Pittet / Douglas A Lauffenburger / Kevin M Haigis

    PLoS Biology, Vol 10, Iss 9, p e

    2012  Volume 1001393

    Abstract: Intestinal epithelial cells exist within a complex environment that affects how they interpret and respond to stimuli. We have applied a multi-scale in vivo systems approach to understand how intestinal immune cells communicate with epithelial cells to ... ...

    Abstract Intestinal epithelial cells exist within a complex environment that affects how they interpret and respond to stimuli. We have applied a multi-scale in vivo systems approach to understand how intestinal immune cells communicate with epithelial cells to regulate responses to inflammatory signals. Multivariate modeling analysis of a large dataset composed of phospho-signals, cytokines, and immune cell populations within the intestine revealed an intimate relationship between immune cells and the epithelial response to TNF-α. Ablation of lymphocytes in the intestine prompted a decrease in the expression of MCP-1, which in turn increased the steady state number of intestinal plasmacytoid dendritic cells (pDCs). This change in the immune compartment affected the intestinal cytokine milieu and subsequent epithelial cell signaling network, with cells becoming hypersensitive to TNF-α-induced apoptosis in a way that could be predicted by mathematical modeling. In summary, we have uncovered a novel cellular network that regulates the response of intestinal epithelial cells to inflammatory stimuli in an in vivo setting.
    Keywords Biology (General) ; QH301-705.5
    Subject code 610
    Language English
    Publishing date 2012-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Correction

    Ken S. Lau / Virna Cortez-Retamozo / Sarah R. Philips / Mikael J. Pittet / Douglas A. Lauffenburger / Kevin M. Haigis

    PLoS Biology, Vol 10, Iss

    Multi-Scale In Vivo Systems Analysis Reveals the Influence of Immune Cells on TNF-α-Induced Apoptosis in the Intestinal Epithelium.

    2012  Volume 10

    Keywords Biology (General) ; QH301-705.5
    Language English
    Publishing date 2012-10-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  3. Article ; Online: Renal intercalated cells sense and mediate inflammation via the P2Y14 receptor.

    Anie Azroyan / Virna Cortez-Retamozo / Richard Bouley / Rachel Liberman / Ye Chun Ruan / Evgeny Kiselev / Kenneth A Jacobson / Mikael J Pittet / Dennis Brown / Sylvie Breton

    PLoS ONE, Vol 10, Iss 3, p e

    2015  Volume 0121419

    Abstract: Uncontrolled inflammation is one of the leading causes of kidney failure. Pro-inflammatory responses can occur in the absence of infection, a process called sterile inflammation. Here we show that the purinergic receptor P2Y14 (GPR105) is specifically ... ...

    Abstract Uncontrolled inflammation is one of the leading causes of kidney failure. Pro-inflammatory responses can occur in the absence of infection, a process called sterile inflammation. Here we show that the purinergic receptor P2Y14 (GPR105) is specifically and highly expressed in collecting duct intercalated cells (ICs) and mediates sterile inflammation in the kidney. P2Y14 is activated by UDP-glucose, a damage-associated molecular pattern molecule (DAMP) released by injured cells. We found that UDP-glucose increases pro-inflammatory chemokine expression in ICs as well as MDCK-C11 cells, and UDP-glucose activates the MEK1/2-ERK1/2 pathway in MDCK-C11 cells. These effects were prevented following inhibition of P2Y14 with the small molecule PPTN. Tail vein injection of mice with UDP-glucose induced the recruitment of neutrophils to the renal medulla. This study identifies ICs as novel sensors, mediators and effectors of inflammation in the kidney via P2Y14.
    Keywords Medicine ; R ; Science ; Q
    Subject code 616
    Language English
    Publishing date 2015-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Regulation of Monocyte Functional Heterogeneity by miR-146a and Relb

    Martin Etzrodt / Virna Cortez-Retamozo / Andita Newton / Jimmy Zhao / Aylwin Ng / Moritz Wildgruber / Pedro Romero / Thomas Wurdinger / Ramnik Xavier / Frederic Geissmann / Etienne Meylan / Matthias Nahrendorf / Filip K. Swirski / David Baltimore / Ralph Weissleder / Mikael J. Pittet

    Cell Reports, Vol 1, Iss 4, Pp 317-

    2012  Volume 324

    Abstract: Monocytes serve as a central defense system against infection and injury but can also promote pathological inflammatory responses. Considering the evidence that monocytes exist in at least two subsets committed to divergent functions, we investigated ... ...

    Abstract Monocytes serve as a central defense system against infection and injury but can also promote pathological inflammatory responses. Considering the evidence that monocytes exist in at least two subsets committed to divergent functions, we investigated whether distinct factors regulate the balance between monocyte subset responses in vivo. We identified a microRNA (miRNA), miR-146a, which is differentially regulated both in mouse (Ly-6Chi/Ly-6Clo) and human (CD14hi/CD14loCD16+) monocyte subsets. The single miRNA controlled the amplitude of the Ly-6Chi monocyte response during inflammatory challenge whereas it did not affect Ly-6Clo cells. miR-146a-mediated regulation was cell-intrinsic and depended on Relb, a member of the noncanonical NF-κB/Rel family, which we identified as a direct miR-146a target. These observations not only provide mechanistic insights into the molecular events that regulate responses mediated by committed monocyte precursor populations but also identify targets for manipulating Ly-6Chi monocyte responses while sparing Ly-6Clo monocyte activity.
    Keywords Biology (General) ; QH301-705.5
    Language English
    Publishing date 2012-04-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Behavior of Endogenous Tumor-Associated Macrophages Assessed In Vivo Using a Functionalized Nanoparticle

    Antoine Leimgruber / Cedric Berger / Virna Cortez-Retamozo / Martin Etzrodt / Andita P. Newton / Peter Waterman / Jose Luiz Figueiredo / Rainer H. Kohler / Natalie Elpek / Thorsten R. Mempel / Filip K. Swirski / Matthias Nahrendorf / Ralph Weissleder / Mikael J. Pittet

    Neoplasia : An International Journal for Oncology Research, Vol 11, Iss 5, Pp 459-

    2009  Volume 468

    Abstract: Tumor-associated macrophages (TAMs) invade the tumor stroma in many cancers, yet their role is incompletely understood. To visualize and better understand these critical cells in tumor progression, we screened a portfolio of rationally selected, ... ...

    Abstract Tumor-associated macrophages (TAMs) invade the tumor stroma in many cancers, yet their role is incompletely understood. To visualize and better understand these critical cells in tumor progression, we screened a portfolio of rationally selected, injectable agents to image endogenous TAMs ubiquitously in three different cancer models (colon carcinoma, lung adenocarcinoma, and soft tissue sarcoma). AMTA680, a functionally derivatized magneto-fluorescent nanoparticle, labeled a subset of myeloid cells with an “M2” macrophage phenotype, whereas other neighboring cells, including tumor cells and a variety of other leukocytes, remained unlabeled. We further show that AMTA680-labeled endogenous TAMs are not altered and can be tracked noninvasively at different resolutions and using various imaging modalities, e.g., fluorescence molecular tomography, magnetic resonance imaging, and multiphoton and confocal intravital microscopy. Quantitative assessment of TAM distribution and activity in vivo identified that these cells cluster in delimited foci within tumors, show relatively low motility, and extend cytoplasmic protrusions for prolonged physical interactions with neighboring tumor cells. Noninvasive imaging can also be used to monitor TAM-depleting regimen quantitatively. Thus, AMTA680 or related cell-targeting agents represent appropriate injectable vehicles for in vivo analysis of the tumor microenvironment.
    Keywords Medicine ; R ; Internal medicine ; RC31-1245 ; Neoplasms. Tumors. Oncology. Including cancer and carcinogens ; RC254-282
    Subject code 610
    Publishing date 2009-05-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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    Inter-library loan at ZB MED

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