Chitosan Interferon-gamma Nanogene Therapy for Lung Disease: Modulation of T-Cell and Dendritic Cell Immune Responses.

: The use of chitosan nanoparticles as carriers for expression plasmids represents a major improvement in gene expression technology. We demonstrated previously that treatment with chitosan interferon-gamma (IFN-gamma) plasmid deoxyribonucleic acid (DNA) nanoparticles (chitosan interferon-gamma nanogene [CIN]) led to in situ production of IFN-gamma and a reduction in inflammation and airway reactivity in mice, but the mechanism underlying the immunomodulatory effects of CIN remains unclear. In this report, the effect of CIN treatment on the immune responses of CD8+ T cells and dendritic cells was examined in a BALB/c mouse model of ovalbumin (OVA)-induced allergic asthma.

Thiolated chitosan/DNA nanocomplexes exhibit enhanced and sustained gene delivery.

Purpose: Thiolated chitosan appears to possess enhanced mucoadhesiveness and cell penetration properties, however, its potential in gene-drug delivery remains unknown. Herein, we report on a highly effective gene delivery system utilizing a 33-kDa thiol-modified chitosan derivative.

Methods: Thiolated chitosan was prepared by the reaction with thioglycolic acid.

Combined fluticasone propionate and salmeterol reduces RSV infection more effectively than either of them alone in allergen-sensitized mice.

Background: Respiratory syncytial virus (RSV) infection is the major cause of bronchiolitis in infants and is a risk factor for the development of asthma. Allergic asthmatics are more susceptible to RSV infection and viral exacerbation.

Methods: Since the effectiveness of corticosteroids in treating RSV infection has been controversial, we tested fluticasone propionate (FP) and salmeterol (Sal) alone versus FP plus Sal (FPS) on RSV-induced airway inflammation.

An immunocompromised BALB/c mouse model for respiratory syncytial virus infection.

Background: Respiratory syncytial virus (RSV) infection causes bronchiolitis in infants and children, which can be fatal, especially in immunocompromised patients. The BALB/c mouse, currently used as a model for studying RSV immunopathology, is semi-permissive to the virus. A mouse model that more closely mimics human RSV infection is needed.

Chitosan IFN-gamma-pDNA Nanoparticle (CIN) Therapy for Allergic Asthma.

BACKGROUND: Allergic subjects produce relatively low amounts of IFN-gamma, a pleiotropic Th-1 cytokine that downregulates Th2-associated airway inflammation and hyperresponsiveness (AHR), the hallmarks of allergic asthma. Adenovirus-mediated IFN-gamma gene transfer reduces AHR, Th2 cytokine levels and lung inflammation in mice, but its use would be limited by the frequency of gene delivery required; therefore, we tested chitosan/IFN-gamma pDNA nanoparticles (CIN) for in situ production of IFN-gamma and its in vivo effects. METHODS: CIN were administered to OVA-sensitized mice to investigate the possibility of using gene transfer to modulate ovalbumin (OVA)-induced inflammation and AHR.

Respiratory syncytial virus infection activates STAT signaling in human epithelial cells.

Acute respiratory syncytial virus (RSV) infection causes airway inflammation and exacerbates asthma, but the mechanism of inflammation is poorly understood. The role of the STAT-signaling pathway in RSV infection in epithelial cells was examined in this study. DNA microarray analyses of RSV-infected human alveolar type II (A549) epithelial cells identified several genes whose expression was altered from -5.

Mechanism of cigarette smoke condensate-induced acute inflammatory response in human bronchial epithelial cells.

Background: To demonstrate the involvement of tobacco smoking in the pathophysiology of lung disease, the responses of pulmonary epithelial cells to cigarette smoke condensate (CSC) - the particulate fraction of tobacco smoke - were examined.

Methods: The human alveolar epithelial cell line A549 and normal human bronchial epithelial cells (NHBEs) were exposed to 0.4 microg/ml CSC, a concentration that resulted in >90% cell survival and <5% apoptosis.