INITIATION AND PROPAGATION OF ASTHMATIC INFLAMMATION

  • Liu, Fu-Tong, (PI)
  • Pan, Xhixing (PI)
  • Croft, Michael (PI)
  • Zuraw, Bruce L. (PI)

Project: Research project

Description

DESCRIPTION (provided by applicant): Unraveling the molecular
mechanisms which promote the development of asthmatic inflammation represents
one of the most challenging and important areas that need to be elucidated in
order to understand this disease. We hypothesize that interactions between
the innate and adaptive immune systems alter airway cells in a manner that
promotes the initiation and propagation of the chronic airway inflammation
associated with the differing asthmatic phenotypes. The individual projects
in this program examine a diverse group of mediators, cytokines, chemokines,
and airway cells. Each project will, however, relate to the central theme and
share substantial commonality in the molecular mechanisms to be studied.
Project 1 will define the molecular events that determine the outcome of
differentiation of naive or uncommitted T cells to T helper (Th)1 or Th2
cells, and the relation of this process to the asthma phenotype. Project 2
will investigate the mechanisms underlying the novel observation that
galectins stimulate chemotaxis of eosinophils and mononuclear phagocytes,
possibly through direct binding to chemokine receptors. Project 3 will
examine the regulatory mechanisms of lipopolysaccharide (LPS) on
cytokine/chemokine synthesis in alveolar macrophages, highlighting the role of
the Toll-like receptor 4 (TLR4) and its downstream signaling pathways.
Project 4 will define the in vivo mechanisms by which kinins stimulate
expression of chemokines and chemokine receptors in human airway epithelial
cells, thereby focusing the recruitment of inflammatory cells to the airway.
Three Cores are proposed for this Asthma and Allergic Diseases Research Center
(AADRC): an Administrative Core A, a Clinical Core B, and an Animal Core C.
A major strength of this Program Project will be the experimental design of
sharing samples (bronchial biopsy and bronchoalveolar fluid) from each subject
among all four projects, allowing the diverse results to be combined into a
comprehensive analysis of the asthmatic phenotype.
This AADRC program is designed to leverage diverse expertise, resources, and
experimental targets into a focused investigation of the origins of asthmatic
inflammation. Taken together these projects may characterize key molecular
mechanisms that contribute to the subsequent chronic inflammatory airway
milieu that is the hallmark of the asthmatic phenotype. Efforts to elucidate
and then modify key events leading to asthmatic inflammation may ultimately be
exploited for prevention of asthmatic disease.
StatusFinished
Effective start/end date9/10/016/30/07

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

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Galectins
Galectin 3
Asthma
Eosinophils
Inflammation
Dimercaprol
Transgenic Mice
Chemotactic Factors
Cytokines
Antigens
Eosinophilia
Immunoglobulin E
Breeding
Monocytes
Immunization
Animal Models
Galactosides
1-Phosphatidylinositol 4-Kinase
Chemokine Receptors
Extracellular Matrix Proteins

Keywords

  • Medicine(all)
  • Immunology and Microbiology(all)