Role of Eosinophils in Airway Inflammation and Remodeling

Summary

Principal Investigator: Nizar N Jarjour
Abstract: DESCRIPTION (provided by applicant): Airway eosinophilia is an important marker of asthma severity, risk of exacerbation, and response to therapy. Based upon the current understanding of the function of eosinophils (EOS), the preliminary data and studies accomplished over the previous funding cycle, form the basis for the hypothesis that EOS play a pivotal role in asthma pathophysiology by enhancing airway inflammation and remodeling. The studies in this PPG renewal application are designed to answer clinically important questions formulated to take maximum advantage of our collective expertise and resources. They will allow us to address critically, comprehensively and interactively the role of EOS in allergic airway inflammation using ex vivo and in vivo experiments in human subjects complemented, as appropriate, by focused use of cell lines and animal models. Project 1 will investigate key EOS functions including promoting IL-17 responses and enhancing fibroblast (Fb) function via expression of SEMA7A, which leads to promoting myoFb differentiation and generation of extracellular matrix (ECM) components. The Th2 skewed environment in the asthmatic airway promotes the expression of periostin, an important marker of allergic inflammation. The proposed studies in Project 2 will determine how this ECM protein interacts with EOS to enhance their survival, mediator release, and response to EOS-active cytokines. Studies will define the requirements for periostin generation in the airway and recognition by the EOS integrin alphaMBeta2. Finally in Project 3, the molecular mechanisms regulating the pro-fibrotic cytokine, TGF-Beta1 signaling in EOS and Fb will be investigated focusing on the role of Pin1 interaction with proximal Smads as well as PI-3-K and Akt. Our group discovered that up-regulation of isomerase Pin1 is an essential step in the TGF-Beta1 signaling pathway and seek to determine how Pin1 influences Smad6 and Smad3 including the role of Akt and PI-3-Kgamma in this process. It can be argued that few other centers, if any, around the world are capable of doing the clinical studies needed to retrieve airway EOS and at the same time have the experience necessary to critically dissect EOS biological functions to the same level of sophistication that our group is capable of doing. The collaborative studies among the three laboratories and the rich clinical research experience will allow us to move back and forth from ex vivo to in vivo experiments to better understand the role of EOS in modulating allergic airway inflammation and remodeling. Given the prominence of eosinophilic inflammation in a significant proportion of severe asthma patients, these advances will have direct implications for the patients most affected by this very common illness.
Funding Period: 2007-04-01 - 2018-03-31
more information: NIH RePORT

Top Publications

  1. pmc Activation states of blood eosinophils in asthma
    M W Johansson
    Department of Biomolecular Chemistry, University of Wisconsin, Madison, WI, USA
    Clin Exp Allergy 44:482-98. 2014
  2. pmc Virus/allergen interactions in asthma
    Monica L Gavala
    Department of Biomolecular Chemistry, School of Medicine and Public Health, University of Wisconsin Madison, Madison, WI 53706, USA
    Curr Allergy Asthma Rep 13:298-307. 2013
  3. pmc Anti-IL-5 attenuates activation and surface density of β(2) -integrins on circulating eosinophils after segmental antigen challenge
    M W Johansson
    Department of Biomolecular Chemistry, University of Wisconsin, Madison, WI, USA
    Clin Exp Allergy 43:292-303. 2013
  4. pmc Segmental allergen challenge enhances chitinase activity and levels of CCL18 in mild atopic asthma
    M L Gavala
    Department of Biomolecular Chemistry, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792 9988, USA
    Clin Exp Allergy 43:187-97. 2013
  5. pmc Rhinitis in older adults
    Sharmilee M Nyenhuis
    Section of Pulmonary, Critical Care, Sleep and Allergy, University of Illinois at Chicago, IL 60611, USA
    Curr Allergy Asthma Rep 13:171-7. 2013
  6. pmc Safety of and cellular response to segmental bronchoprovocation in allergic asthma
    Loren C Denlinger
    Allergy, Pulmonary and Critical Care Division, Department of Medicine, University of Wisconsin, Madison, WI, USA
    PLoS ONE 8:e51963. 2013
  7. pmc α(M)β(2) integrin-mediated adhesion and motility of IL-5-stimulated eosinophils on periostin
    Mats W Johansson
    Department of Biomolecular Chemistry, University of Wisconsin, Madison, WI 53706, USA
    Am J Respir Cell Mol Biol 48:503-10. 2013
  8. pmc The role of autoimmune testing in chronic idiopathic urticaria
    Ravi K Viswanathan
    Division of Allergy, Pulmonary and Critical Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin Department of Medicine, William S Middleton Veterans Hospital, Madison, Wisconsin
    Ann Allergy Asthma Immunol 108:337-341.e1. 2012
  9. pmc Potent synergistic effect of IL-3 and TNF on matrix metalloproteinase 9 generation by human eosinophils
    Elizabeth A B Kelly
    Allergy, Pulmonary and Critical Care Medicine Division, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA
    Cytokine 58:199-206. 2012
  10. pmc Lactoferrin regulates an axis involving CD11b and CD49d integrins and the chemokines MIP-1α and MCP-1 in GM-CSF-treated human primary eosinophils
    Colleen S Curran
    Department of Molecular Biology, University of Wisconsin, Madison, Wisconsin 53706, USA
    J Interferon Cytokine Res 32:450-61. 2012

Research Grants

  1. Mechanisms of Atherogenesis in Insulin Resistance
    IRA A TABAS; Fiscal Year: 2013
  2. DIABETES AND ENDOCRINOLOGY RESEARCH CENTER
    Domenico Accili; Fiscal Year: 2013
  3. LIPID AND LIPOPROTEIN METABOLISM IN ATHEROSCLEROSIS
    Alan M Fogelman; Fiscal Year: 2013
  4. EARLY EVENTS IN ALZHEIMER PATHOGENESIS
    SUE TILTON GRIFFIN; Fiscal Year: 2013
  5. Pathophysiology of Alveolar Epithelial Lung Injury
    Jacob I Sznajder; Fiscal Year: 2013
  6. Inflammatory responses of vascular cells
    Paul L Fox; Fiscal Year: 2013
  7. Neurohumoral control of veins in hypertension
    Gregory D Fink; Fiscal Year: 2013
  8. INTEGRATED MECHANISMS OF CARDIAC MALADAPTATION
    R John Solaro; Fiscal Year: 2013
  9. Regulatory Mechanisms In Intestinal Motility
    Kenton M Sanders; Fiscal Year: 2013
  10. Cardiac Fibrillation: Mechanisms and Therapy
    James N Weiss; Fiscal Year: 2013

Detail Information

Publications55

  1. pmc Activation states of blood eosinophils in asthma
    M W Johansson
    Department of Biomolecular Chemistry, University of Wisconsin, Madison, WI, USA
    Clin Exp Allergy 44:482-98. 2014
    ..The association with lung function does not occur in severe asthma, presumably due to greater eosinophil extravasation, specifically of activated or pre-activated cells, in severe disease...
  2. pmc Virus/allergen interactions in asthma
    Monica L Gavala
    Department of Biomolecular Chemistry, School of Medicine and Public Health, University of Wisconsin Madison, Madison, WI 53706, USA
    Curr Allergy Asthma Rep 13:298-307. 2013
    ..One or more of these processes may provide targets for new therapeutics to treat allergic asthma and prevent disease exacerbation...
  3. pmc Anti-IL-5 attenuates activation and surface density of β(2) -integrins on circulating eosinophils after segmental antigen challenge
    M W Johansson
    Department of Biomolecular Chemistry, University of Wisconsin, Madison, WI, USA
    Clin Exp Allergy 43:292-303. 2013
    ..IL-5 activates α(M) β(2) integrin on blood eosinophils in vitro. Eosinophils in bronchoalveolar lavage (BAL) following segmental antigen challenge have activated β(2) -integrins...
  4. pmc Segmental allergen challenge enhances chitinase activity and levels of CCL18 in mild atopic asthma
    M L Gavala
    Department of Biomolecular Chemistry, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792 9988, USA
    Clin Exp Allergy 43:187-97. 2013
    ..CCL18, chitotriosidase (CHIT1) and YKL-40 are readily detectable in the lungs and contribute to remodelling in other fibrotic diseases, but their involvement in allergic asthma is unclear...
  5. pmc Rhinitis in older adults
    Sharmilee M Nyenhuis
    Section of Pulmonary, Critical Care, Sleep and Allergy, University of Illinois at Chicago, IL 60611, USA
    Curr Allergy Asthma Rep 13:171-7. 2013
    ..Environmental changes and avoidance measures are a primary means of intervention. In addition, there are several topical therapies (nasal sprays) that can be effective for symptom control...
  6. pmc Safety of and cellular response to segmental bronchoprovocation in allergic asthma
    Loren C Denlinger
    Allergy, Pulmonary and Critical Care Division, Department of Medicine, University of Wisconsin, Madison, WI, USA
    PLoS ONE 8:e51963. 2013
    ..Despite its incorporation into research studies, the safety aspects of segmental allergen bronchoprovocation and differences in cellular response among different allergens have received limited consideration...
  7. pmc α(M)β(2) integrin-mediated adhesion and motility of IL-5-stimulated eosinophils on periostin
    Mats W Johansson
    Department of Biomolecular Chemistry, University of Wisconsin, Madison, WI 53706, USA
    Am J Respir Cell Mol Biol 48:503-10. 2013
    ....
  8. pmc The role of autoimmune testing in chronic idiopathic urticaria
    Ravi K Viswanathan
    Division of Allergy, Pulmonary and Critical Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin Department of Medicine, William S Middleton Veterans Hospital, Madison, Wisconsin
    Ann Allergy Asthma Immunol 108:337-341.e1. 2012
    ..The clinical implications of autoimmune testing in chronic idiopathic urticaria (CIU) are not well established...
  9. pmc Potent synergistic effect of IL-3 and TNF on matrix metalloproteinase 9 generation by human eosinophils
    Elizabeth A B Kelly
    Allergy, Pulmonary and Critical Care Medicine Division, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA
    Cytokine 58:199-206. 2012
    ....
  10. pmc Lactoferrin regulates an axis involving CD11b and CD49d integrins and the chemokines MIP-1α and MCP-1 in GM-CSF-treated human primary eosinophils
    Colleen S Curran
    Department of Molecular Biology, University of Wisconsin, Madison, Wisconsin 53706, USA
    J Interferon Cytokine Res 32:450-61. 2012
    ..Thus, LF release at sites of inflammation may alter eosinophil recruitment/activation and possibly the progression of diseases such as cancer and asthma where significant eosinophil influx has been described...
  11. pmc Human eosinophils release IL-1ß and increase expression of IL-17A in activated CD4+ T lymphocytes
    S Esnault
    Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA
    Clin Exp Allergy 42:1756-64. 2012
    ..We have shown that eosinophils (EOS) have the potential to influence Th1 and Th2 cytokine generation by CD4(+) cells, but their influence on IL-17A (IL-17) has not been established...
  12. pmc Rhinovirus-induced IL-1β release from bronchial epithelial cells is independent of functional P2X7
    Lei Shi
    Division of Allergy, Pulmonary and Critical Care Medicine, University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, CSC Box 9988, Madison, WI 53792, USA
    Am J Respir Cell Mol Biol 47:363-71. 2012
    ..These results support the expression of functional P2X(7) in human lung epithelium, although its role in epithelial pathogen defense is likely independent of IL-1 family cytokine processing...
  13. pmc Pin1-FADD interactions regulate Fas-mediated apoptosis in activated eosinophils
    Jiyoung Oh
    Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390 9072, USA
    J Immunol 190:4937-45. 2013
    ..Therefore, our data suggest that Pin1 is a critical link between FADD-mediated cell death and IL-5-mediated prosurvival signaling...
  14. pmc Pin1 null mice exhibit low bone mass and attenuation of BMP signaling
    Zhong Jian Shen
    Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America
    PLoS ONE 8:e63565. 2013
    ..Our results thus uncover a novel aspect of the molecular underpinning of osteoblast function and identify a new therapeutic target for bone diseases...
  15. pmc Interaction between allergy and innate immunity: model for eosinophil regulation of epithelial cell interferon expression
    Sameer K Mathur
    Division of Allergy, Pulmonary and Critical Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53792, USA
    Ann Allergy Asthma Immunol 111:25-31. 2013
    ..Eosinophils in asthmatic airways are associated with risk of exacerbations. The most common cause of asthma exacerbations is viral respiratory infections, particularly human rhinovirus (HRV)...
  16. pmc Semaphorin 7A is expressed on airway eosinophils and upregulated by IL-5 family cytokines
    Stephane Esnault
    Department of Medicine, Allergy, Pulmonary, and Critical Care Medicine Division, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA Electronic address
    Clin Immunol 150:90-100. 2014
    ..semaphorin 7A is a potentially important modulator of eosinophil profibrotic functions in the airway remodeling of patients with chronic asthma. ..
  17. pmc Interferon gene expression in sputum cells correlates with the Asthma Index Score during virus-induced exacerbations
    E A Schwantes
    Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
    Clin Exp Allergy 44:813-21. 2014
    ..The majority of asthma exacerbations are related to viral respiratory infections. Some, but not all, previous studies have reported that low interferon responses in patients with asthma increase the risk for virus-induced exacerbations...
  18. pmc Relevance of allergy in adult asthma
    Sameer K Mathur
    University of Wisconsin School of Medicine, Madison, WI, USA
    Curr Allergy Asthma Rep 14:437. 2014
    ..In addition, this review will address whether therapies targeted at the atopic axis help improve asthma outcomes, including lung function indices and exacerbations. ..
  19. pmc Retrospective analysis of the efficacy of omalizumab in chronic refractory urticaria
    Ravi K Viswanathan
    Division of Allergy, Pulmonary and Critical Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA
    Allergy Asthma Proc 34:446-52. 2013
    ..Our study shows that omalizumab has robust efficacy in refractory CU patients regardless of their autoimmune status, age, gender, IgE levels, or dosing protocol. ..
  20. pmc IL-5 induces suspended eosinophils to undergo unique global reorganization associated with priming
    Shih Tsung Han
    Departments of 1 Biomolecular Chemistry and
    Am J Respir Cell Mol Biol 50:654-64. 2014
    ....
  21. pmc Autotaxin production of lysophosphatidic acid mediates allergic asthmatic inflammation
    Gye Young Park
    1 Section of Pulmonary, Critical Care, Sleep, and Allergy, Department of Medicine
    Am J Respir Crit Care Med 188:928-40. 2013
    ....
  22. pmc Human airway eosinophils exhibit preferential reduction in STAT signaling capacity and increased CISH expression
    Mandy E Burnham
    Department of Biomolecular Chemistry, School of Medicine and Public Health, University of Wisconsin Madison, Madison, WI 53792, USA
    J Immunol 191:2900-6. 2013
    ..These data support a model in which IL-5 family cytokines trigger a selective downregulation mechanism in EOS(A) for JAK/STAT pathways...
  23. pmc Identification of genes expressed by human airway eosinophils after an in vivo allergen challenge
    Stephane Esnault
    Department of Medicine, Allergy, Pulmonary, and Critical Care Medicine Division, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA
    PLoS ONE 8:e67560. 2013
    ..Genome-wide expression analysis of airway EOS by microarrays has been limited by the ability to generate high quality RNA from sufficient numbers of airway EOS...
  24. pmc Markers of vascular perturbation correlate with airway structural change in asthma
    Mats W Johansson
    Department of Biomolecular Chemistry, University of Wisconsin, 4285A Medical Sciences Center, 1300 University Avenue, Madison, WI 53706, USA
    Am J Respir Crit Care Med 188:167-78. 2013
    ..Vascular endothelial cell products have not been explored as a surrogate to mark structural airway changes in asthma...
  25. pmc The C-terminus of human nucleotide receptor P2X7 is critical for receptor oligomerization and N-linked glycosylation
    Lisa E Wickert
    Department of Biomolecular Chemistry, The University of Wisconsin Madison, Madison, Wisconsin, USA
    PLoS ONE 8:e63789. 2013
    ..Mutations within the trafficking domain result in attenuated receptor activity and cell surface presentation, but the mechanisms by which amino acid changes within this region promote altered P2X7 function have not been elucidated...
  26. pmc Platelet activation, P-selectin, and eosinophil β1-integrin activation in asthma
    Mats W Johansson
    Department of Biomolecular Chemistry, University of Wisconsin, Madison, 53706, USA
    Am J Respir Crit Care Med 185:498-507. 2012
    ..Eosinophil β1-integrin activation correlates inversely with FEV1 and directly with eosinophil-bound P-selectin in subjects with nonsevere allergic asthma...
  27. pmc Quantitative microtiter fibronectin fibrillogenesis assay: use in high throughput screening for identification of inhibitor compounds
    Bianca R Tomasini-Johansson
    University of Wisconsin Madison, Department of Biomolecular Chemistry and Medicine, Madison, WI 53706, United States
    Matrix Biol 31:360-7. 2012
    ..Screening of more diverse chemical libraries and identification of specific and efficient modulators of FN fibrillogenesis may result in therapeutics to control excessive connective tissue deposition...
  28. pmc A sensitive high throughput ELISA for human eosinophil peroxidase: a specific assay to quantify eosinophil degranulation from patient-derived sources
    Sergei I Ochkur
    Division of Pulmonary Medicine, Department of Biochemistry and Molecular Biology, Mayo Clinic Arizona, Scottsdale, AZ, USA
    J Immunol Methods 384:10-20. 2012
    ..In addition, this assay is adaptable to high throughput formats (e.g., automated assays utilizing microtiter plates) using the diverse patient fluid samples typically available in research and clinical settings...
  29. pmc Human airway eosinophils respond to chemoattractants with greater eosinophil-derived neurotoxin release, adherence to fibronectin, and activation of the Ras-ERK pathway when compared with blood eosinophils
    Mary Ellen Bates
    Department of Biomolecular Chemistry, University of Wisconsin, Madison, WI 53706, USA
    J Immunol 184:7125-33. 2010
    ..Human airway eosinophils respond to several chemoattractants with increased activation of the Ras-ERK cascade, eosinophil-derived neurotoxin release, and adherence to fibronectin relative to blood eosinophils...
  30. pmc The prolyl isomerase Pin1 acts as a novel molecular switch for TNF-alpha-induced priming of the NADPH oxidase in human neutrophils
    Tarek Boussetta
    INSERM U773, Paris, France
    Blood 116:5795-802. 2010
    ..These findings indicate that Pin1 is critical for TNF-α-induced priming of NADPH oxidase and for excessive ROS production. Pin1 inhibition could potentially represent a novel anti-inflammatory strategy...
  31. pmc Mutation of putative N-linked glycosylation sites on the human nucleotide receptor P2X7 reveals a key residue important for receptor function
    Lisa Y Lenertz
    Department of Biomolecular Chemistry, The University of Wisconsin, Madison, Wisconsin 53706, USA
    Biochemistry 49:4611-9. 2010
    ..This is the first report to map human P2X(7) glycosylation sites and reveal residue N187 is critical for receptor trafficking and function...
  32. pmc The peptidyl-prolyl isomerase Pin1 facilitates cytokine-induced survival of eosinophils by suppressing Bax activation
    Zhong Jian Shen
    Waisman Center for Developmental Disabilities, The Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53705, USA
    Nat Immunol 10:257-65. 2009
    ..Our findings indicate that Pin1 is a key mediator of prosurvival signaling and is a regulator of Bax function...
  33. pmc Potential contribution of IL-7 to allergen-induced eosinophilic airway inflammation in asthma
    Elizabeth A B Kelly
    Section of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA
    J Immunol 182:1404-10. 2009
    ..Activation of eosinophils is a novel function for IL-7...
  34. pmc Cell signaling via the P2X(7) nucleotide receptor: linkage to ROS production, gene transcription, and receptor trafficking
    Lisa Y Lenertz
    Department of Biomolecular Chemistry, University of Wisconsin Madison, Madison, WI, 53706, USA
    Purinergic Signal 5:175-87. 2009
    ..Altogether, these data further implicate P2X(7) activation and signaling as a fundamental modulator of macrophage immune responses...
  35. pmc Role of insulin-like growth factor binding protein-3 in allergic airway remodeling
    Kristen L Veraldi
    Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA
    Am J Respir Crit Care Med 180:611-7. 2009
    ....
  36. doi Thymic stromal lymphopoietin expression in allergic pulmonary inflammation is Pin1-dependent
    Stephane Esnault
    J Allergy Clin Immunol 121:1289-90. 2008
  37. pmc Up-regulation and activation of eosinophil integrins in blood and airway after segmental lung antigen challenge
    Mats W Johansson
    Department of Biomolecular Chemistry, University of Wisconsin, Madison, WI53706, USA
    J Immunol 180:7622-35. 2008
    ..Finally, eosinophils present in IL-5-rich airway fluid have a hyperadhesive phenotype associated with increased surface expression of alpha(M)beta(2) and activation of beta(2) integrins...
  38. pmc The Pin 1 inhibitor juglone attenuates kidney fibrogenesis via Pin 1-independent mechanisms in the unilateral ureteral occlusion model
    Shannon Reese
    Departments of Medicine and Surgery, University of Wisconsin Madison School of Medicine and Public Health, Madison, WI, USA
    Fibrogenesis Tissue Repair 3:1. 2010
    ....
  39. pmc Human monocytic cells direct the robust release of CXCL10 by bronchial epithelial cells during rhinovirus infection
    N L Korpi-Steiner
    Department of Biomolecular Chemistry, Division of Allergy and Immunology, University of Wisconsin Madison, Madison, WI 53706 0450, USA
    Clin Exp Allergy 40:1203-13. 2010
    ..As HRV-induced cytokine levels in vivo are markedly elevated, this observation suggests that other mechanisms independent of direct viral infection may induce epithelial cell cytokine release...
  40. pmc Pin1 protein regulates Smad protein signaling and pulmonary fibrosis
    Zhong Jian Shen
    Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53706, USA
    J Biol Chem 287:23294-305. 2012
    ..Therefore, Pin1 is essential for normal Smad6 function and ECM production in response to injury or TGF-β and thus may be an attractive therapeutic target to prevent excess scarring in diverse lung diseases...
  41. pmc IGD motifs, which are required for migration stimulatory activity of fibronectin type I modules, do not mediate binding in matrix assembly
    Lisa M Maurer
    Departments of Biomolecular Chemistry and Medicine, University of Wisconsin Madison, Madison, Wisconsin, United States of America
    PLoS ONE 7:e30615. 2012
    ..These results suggest that the picomolar interactions of 70K with cells that stimulate cell migration require different conformations of FNI modules than the nanomolar interactions required for assembly...
  42. pmc Human eosinophils express RAGE, produce RAGE ligands, exhibit PKC-delta phosphorylation and enhanced viability in response to the RAGE ligand, S100B
    Colleen S Curran
    Department of Biomolecular Chemistry, University of Wisconsin, Madison, WI 53706, USA
    Int Immunol 23:713-28. 2011
    ..The expression of eosinophil RAGE, soluble RAGE and RAGE ligands may be pivotal to the functions of eosinophils in various human diseases involving RAGE and S100 ligands...
  43. pmc Activation of beta1 integrins on blood eosinophils by P-selectin
    Mats W Johansson
    Department of Biomolecular Chemistry, University of Wisconsin, 4285A, Medical Sciences Center, 1300 University Avenue, Madison, WI 53706, USA
    Am J Respir Cell Mol Biol 45:889-97. 2011
    ....
  44. pmc GM-CSF production by glioblastoma cells has a functional role in eosinophil survival, activation, and growth factor production for enhanced tumor cell proliferation
    Colleen S Curran
    Department of Animal Health and Biomedical Sciences, University of Wisconsin, Madison, WI 53706, USA
    J Immunol 187:1254-63. 2011
    ..These data support the idea of a paracrine loop between GM-CSF-producing tumors and eosinophil-derived growth factors in tumor promotion/progression...
  45. pmc Role of allergen sensitization in older adults
    Ravi K Viswanathan
    Division of Allergy, Pulmonary and Critical Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, K4 952 CSC, 600 Highland Avenue, Madison, WI 53792, USA
    Curr Allergy Asthma Rep 11:427-33. 2011
    ..Consequently, an appropriate evaluation of allergic sensitivities is warranted and indicated in older asthma and rhinitis patients to provide optimal care for the individual and minimize any resultant morbidity and mortality...
  46. pmc Chemoattractant-induced signaling via the Ras-ERK and PI3K-Akt networks, along with leukotriene C4 release, is dependent on the tyrosine kinase Lyn in IL-5- and IL-3-primed human blood eosinophils
    Yiming Zhu
    Molecular and Cellular Pharmacology Program, University of Wisconsin, Madison, WI 53706, USA
    J Immunol 186:516-26. 2011
    ....
  47. pmc Transcriptional control mechanisms associated with the nucleotide receptor P2X7, a critical regulator of immunologic, osteogenic, and neurologic functions
    Lisa Y Lenertz
    Department of Biomolecular Chemistry, School of Medicine and Public Health, The University of Wisconsin Madison, 53706, USA
    Immunol Res 50:22-38. 2011
    ....
  48. pmc Age-related changes in immune function: effect on airway inflammation
    Paula J Busse
    Division of Clinical Immunology, Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA
    J Allergy Clin Immunol 126:690-9; quiz 700-1. 2010
    ..This review examines specific innate and adaptive immune responses affected by aging that might affect the inflammatory response in older adults with asthma...
  49. pmc Role of infection in the development and exacerbation of asthma
    Theresa W Guilbert
    Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, K4 944, CSC 4108, Madison, WI 53792, USA
    Expert Rev Respir Med 4:71-83. 2010
    ..This review discusses these various associations as they pertain to the development and exacerbation of asthma...
  50. pmc The nucleotide receptor P2RX7 mediates ATP-induced CREB activation in human and murine monocytic cells
    Monica L Gavala
    Department of Biomolecular Chemistry, University of Wisconsin, Madison, WI 53706, USA
    J Leukoc Biol 84:1159-71. 2008
    ..These studies support the idea that P2RX7 stimulation can directly regulate protein expression that is not dependent on costimulation with other immune modulators such as LPS...

Research Grants30

  1. Mechanisms of Atherogenesis in Insulin Resistance
    IRA A TABAS; Fiscal Year: 2013
    ..End of Abstract) ..
  2. DIABETES AND ENDOCRINOLOGY RESEARCH CENTER
    Domenico Accili; Fiscal Year: 2013
    ....
  3. LIPID AND LIPOPROTEIN METABOLISM IN ATHEROSCLEROSIS
    Alan M Fogelman; Fiscal Year: 2013
    ..These six Projects will be supported by four cores and together will form a highly interactive and synergistic Program Project that is focused on lipid and lipoprotein metabolism in atherosclerosis. ..
  4. EARLY EVENTS IN ALZHEIMER PATHOGENESIS
    SUE TILTON GRIFFIN; Fiscal Year: 2013
    ..The synergy between our aims, approaches, and measures will enable us to meet our goal of defining early cellular interactions toward development of rational interventions in AD. ..
  5. Pathophysiology of Alveolar Epithelial Lung Injury
    Jacob I Sznajder; Fiscal Year: 2013
    ..The insights gained from the data generated from these studies will provide novel molecular targets for the development of new therapeutic strategies to treat patients with lung injury. ..
  6. Inflammatory responses of vascular cells
    Paul L Fox; Fiscal Year: 2013
    ..abstract_text> ..
  7. Neurohumoral control of veins in hypertension
    Gregory D Fink; Fiscal Year: 2013
    ..This project tests the idea that altered structure or function of veins also may cause hypertension, and that it may be possible to treat hypertension using drugs that affect veins. ..
  8. INTEGRATED MECHANISMS OF CARDIAC MALADAPTATION
    R John Solaro; Fiscal Year: 2013
    ..Studies proposed here offer the potential for novel diagnostic procedures early in the progression of the disorders, and targets for novel therapies. (End of Abstract) ..
  9. Regulatory Mechanisms In Intestinal Motility
    Kenton M Sanders; Fiscal Year: 2013
    ..The investigative team is highly synergistic and collaborative, and the PPG has a long track-record of productivity and novel discovery ..
  10. Cardiac Fibrillation: Mechanisms and Therapy
    James N Weiss; Fiscal Year: 2013
    ..Together, these studies will provide critical groundwork necessary to develop and advance novel therapies for this major complication and cause of mortality from heart disease. ..