Mast cell and Airway Remodeling

University Of California, San Diego, La Jolla CA

Investigators

Linked publications & trials

Abstract

We propose to use a mouse model of allergen induced airway remodeling to investigate the contribution of[unreadable] mast cells to airway remodeling, as well as to understand the mechanism by which mast cell progenitors[unreadable] traffic from the bone marrow to the lung and contribute to airway remodeling. In particular we hypothesize[unreadable] that mast cell derived TNF plays a central role in mediating allergen induced airway remodeling through[unreadable] effects on airway smooth muscle, as well as through recruitment of mast cell progenitors and eosinophils to[unreadable] the lung. To test this hypothesis we plan to determine levels of allergen induced airway remodeling in WT[unreadable] mice and compare this to levels noted in mutant mice (mast cell deficient, TNF deficient), as well as mast[unreadable] cell deficient mice reconstituted with TNF deficient mast cells. In addition, we have utilized cre/lox molecular[unreadable] techniques to generate mice deficient in the ability to activate NF-kB in airway epithelium. As these mutant[unreadable] mice exhibit reduced numbers of peribronchial mast cells, they will be utilized to investigate the role of NFkB[unreadable] regulated genes in airway epithelium contributing to mast cell progenitor trafficking to the remodeled[unreadable] airway. Overall, these studies will provide insight into the mechanism by which mast cell derived TNF[unreadable] contributes to airway remodeling, as well improve our understanding of the mechanism by which NF-kB[unreadable] regulated genes in airway epithelium direct mast cell progenitor trafficking from the bone marrow to the lung[unreadable] and contribute to airway remodeling.[unreadable] TNF is a protein that is highly expressed in the airway in asthmatics with ongoing symptoms of asthma. Our[unreadable] studies in a mouse model will shed light on whether therapies targeting TN in asthma may provide a novel[unreadable] strategy to reduce airway scarring in severe asthmatics.