The effect of CD95 ligand gene on airway inflammation and immune effector cells in a murine model of asthma
Date Issued
2004
Date
2004
Author(s)
Chuang, Ya-Hui
DOI
en-US
Abstract
Allergic asthma is characterized by airway hyperresponsiveness, high serum IgE levels, and cellular infiltration of the airway with predominantly eosinophils and T cells expressing a type 2 T helper (Th2) profile of cytokines. Th2 cells are crucial for the initiation and progression of allergic asthma. The normal resolution of inflammation in the lung occurs through the regulated removal of unneeded cells by Fas-Fas ligand mediated apoptosis. Asthmatics are found to be associated with reduced apoptosis of inflammatory cells such as eosinophils and lymphocytes in the lung. Fas ligand (FasL) is a member of the tumor necrosis factor family, and when bound to Fas, it induces apoptosis of the cells. In the present study, we attempted to clarify whether the induction of apoptosis is beneficial in asthma and to examine the effect of FasL gene on airway inflammation and immune effector cells in allergic asthma. To this end, recombinant adenovirus expressing murine FasL (Ad-FasL) and dendritic cells (DC) genetically engineered to express FasL (DC-FasL) were delivered into allergic mice and asthma manifestations were measured. We found that a single intratracheally administration of Ad-FasL in OVA-immunized mice significantly alleviated airway hyperresponsiveness and eosinophilia by inducing the apoptosis of eosinophils and/or reducing eosinophil attractant factors, such as IL-5 and eotaxin levels. The number of infiltrated lymphocytes and Th2 cytokines, including IL-5 and IL-13, decreased in OVA-immunized mice by administration of Ad-FasL. KC and TNF-
Subjects
樹突細胞, OVA特異性T 細胞,腺病毒載體, 細胞凋亡,嗜酸性白血球
dendritic cell, OVA-specific T cells, adenoviral v
Type
other