Abstract

This application will study the biology of IL-13 and two new CC chemokines, C10 and MDC in the pathogenesis of sepsis following cecal ligation and puncture (CLP) in mice. Cytokine networks are critical in the host response to peritonitis and other forms of sepsis. The major hypothesis is that during the evolution of sepsis, IL-13 and CC chemokines induced by IL-13 regulate the host response and protect the host from organ injury. This hypothesis will be explored in 4 specific aims using a murine model of cecal-ligation and puncture (CLP) in mice.
Aim 1 will investigate the expression and tissue distribution of IL-13.
Aim 2 will investigate the role of IL-13 in the pathogenesis of sepsis using several different strategies to neutralize IL-13.
Aim 3 will investigate the expression and role of MDC and C10 in sepsis using methods similar to those in Aims 1 and 2.
Aim 4 will use transgenic mice to explore the role of STAT6 as a key signaling molecule in the pathogenesis of sepsis in CLP. These studies will provide new information about the key roles of IL-13 and CC chemokines in the pathogenesis of the systemic response induced by CLP in mice.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL031237-18
Application #
6530624
Study Section
Special Emphasis Panel (ZRG1-RAP (01))
Program Officer
Harabin, Andrea L
Project Start
1984-01-01
Project End
2004-02-28
Budget Start
2002-03-01
Budget End
2003-02-28
Support Year
18
Fiscal Year
2002
Total Cost
$295,880
Indirect Cost

  Institution

Name
University of Michigan Ann Arbor
Department
Pathology
Type
Schools of Medicine
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109

  Publications

Carson 4th, William F; Cavassani, Karen A; Soares, Elyara M et al. (2017) The STAT4/MLL1 Epigenetic Axis Regulates the Antimicrobial Functions of Murine Macrophages. J Immunol 199:1865-1874
Carson 4th, William F; Salter-Green, Sarah E; Scola, Melissa M et al. (2017) Enhancement of macrophage inflammatory responses by CCL2 is correlated with increased miR-9 expression and downregulation of the ERK1/2 phosphatase Dusp6. Cell Immunol 314:63-72
Ito, Toshihiro; Itakura, Junya; Takahashi, Sakuma et al. (2016) Sprouty-Related Ena/Vasodilator-Stimulated Phosphoprotein Homology 1-Domain-Containing Protein-2 Critically Regulates Influenza A Virus-Induced Pneumonia. Crit Care Med 44:e530-43
Kovach, Melissa A; Singer, Benjamin H; Newstead, Michael W et al. (2016) IL-36? is secreted in microparticles and exosomes by lung macrophages in response to bacteria and bacterial components. J Leukoc Biol 100:413-21
Podsiad, Amy; Standiford, Theodore J; Ballinger, Megan N et al. (2016) MicroRNA-155 regulates host immune response to postviral bacterial pneumonia via IL-23/IL-17 pathway. Am J Physiol Lung Cell Mol Physiol 310:L465-75
Kroetz, Danielle N; Allen, Ronald M; Schaller, Matthew A et al. (2015) Type I Interferon Induced Epigenetic Regulation of Macrophages Suppresses Innate and Adaptive Immunity in Acute Respiratory Viral Infection. PLoS Pathog 11:e1005338
Carson 4th, William F; Guernsey, Linda A; Singh, Anurag et al. (2015) Cbl-b Deficiency in Mice Results in Exacerbation of Acute and Chronic Stages of Allergic Asthma. Front Immunol 6:592
Dewyer, Nicholas A; El-Sayed, Osama M; Luke, Catherine E et al. (2015) Divergent effects of Tlr9 deletion in experimental late venous thrombosis resolution and vein wall injury. Thromb Haemost 114:1028-37
Schaller, Matthew; Ito, Toshihiro; Allen, Ronald M et al. (2015) Epigenetic regulation of IL-12-dependent T cell proliferation. J Leukoc Biol 98:601-13
Kittan, Nicolai A; Allen, Ronald M; Dhaliwal, Abhay et al. (2013) Cytokine induced phenotypic and epigenetic signatures are key to establishing specific macrophage phenotypes. PLoS One 8:e78045

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