Adenovirus expressing Fas ligand gene decreases airway hyper-responsiveness and eosinophilia in a murine model of asthma.
Allergic asthma is characterized by airway hyper-responsiveness (AHR) and cellular infiltration of the airway with predominantly eosinophils and Th2 cells. The normal resolution of inflammation in the lung occurs through the regulated removal of unneeded cells by Fas-Fas ligand-mediated apoptosis. Fas ligand (FasL) is a member of the tumor necrosis factor family, and when bound to Fas, it induces apoptosis of the cells. To examine the effect of the FasL gene on airway inflammation and immune effector cells in allergic asthma, recombinant adenovirus expressing murine FasL (Ad-FasL) was delivered intratracheally into ovalbumin (OVA)-immunized mice. We found that a single administration of Ad-FasL in OVA-immunized mice significantly alleviated AHR 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-alpha production also decreased in Ad-FasL-treated OVA-immunized mice. These findings indicated that the administration of Ad-FasL to OVA-sensitized mice significantly suppressed pulmonary allergic responses. Although more studies are needed, these results suggested that Ad-FasL might be applied as an alternative therapy for allergic asthma.
Chuang
Y-H
YH
Graduate Institute of Immunology, Taipei, Taiwan, Republic of China.
Fu
C-L
CL
Lo
Y-C
YC
Chiang
B-L
BL
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D001249:Asthma / Q000276:immunology / Q000628:therapy*; D016535:Bronchial Hyperreactivity; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D053222:Fas Ligand Protein; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000235:genetics; D007958:Leukocyte Count; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D020545:Respiratory Mucosa / Q000276:immunology*; D014161:Transduction, Genetic / Q000379:methods
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins