ABSTRACT
Foxp3 is a master regulator of CD4(+)CD25(+) regulatory T-cell (Treg) function and is also a suppressor of SKP2 and HER2/ErbB2. There are an increasing number of reports describing the functions of Foxp3 in cell types other than Tregs. In this context, we evaluated the functions of Foxp3 in ovalbumin- and cockroach-induced asthma models. Foxp3-EGFP-expressing adenovirus or EGFP control adenovirus was administered intratracheally (i.t.), followed by challenge with ovalbumin (OVA) or cockroach extract to induce asthma. Th2 cytokine and immune cell profiles of bronchoalveolar lavage fluid (BALF), as well as serum IgE levels, were analyzed. Histological analyses were also conducted to demonstrate the effects of Foxp3 expression on airway remodeling, goblet cell hyperplasia and inflammatory responses in the lung. Adenoviral Foxp3 was expressed only in lung epithelial cells, and not in CD4(+) or CD8(+) cells. BALF from Foxp3 gene-delivered mice showed significantly reduced numbers of total immune cells, eosinophils, neutrophils, macrophages and lymphocytes in response to cockroach allergen or OVA. In addition, Foxp3 expression in the lung reduced the levels of Th2 cytokines and IgE in BALF and serum, respectively. Moreover, histopathological analysis also showed that Foxp3 expression substantially inhibited eosinophil infiltration into the airways, goblet cell hyperplasia and smooth muscle cell hypertrophy. Furthermore, when Tregs were depleted by diphtheria toxin in Foxp3(DTR) mice, the anti-asthmatic functions of Foxp3 were not altered in OVA-challenged asthma models. In this study, our results suggest that Foxp3 expression in lung epithelial cells, and not in Tregs, inhibited OVA- and cockroach extract-induced asthma.
Subject(s)
Adenoviridae/genetics , Asthma/genetics , Asthma/therapy , Forkhead Transcription Factors/genetics , Lung/pathology , Respiratory Mucosa/pathology , Animals , Asthma/immunology , Asthma/pathology , Cockroaches/immunology , Cytokines/analysis , Cytokines/immunology , Female , Forkhead Transcription Factors/immunology , Genetic Therapy , Lung/immunology , Lung/metabolism , Mice, Inbred C57BL , Ovalbumin/immunology , Respiratory Mucosa/immunology , Respiratory Mucosa/metabolism , T-Lymphocytes, Regulatory/immunology , T-Lymphocytes, Regulatory/metabolism , T-Lymphocytes, Regulatory/pathologyABSTRACT
BACKGROUND: Alzheimer's disease (AD) is the most common cause of dementia. This disease is a progressive and irreversible brain disorder accompanied with severe learning and memory impairment. This study investigated whether treatment with standardized Lycii Fructus Extract (LFE) would improve the cognitive function and the pathological features of AD in 3xTg-AD mice. ETHNOPHARMACOLOGICAL RELEVANCE: Lycii Fructus is a fruit of Lycium chinense Miller and widely distributed in East Asia and has been used traditionally for anti-aging purposes. MATERIALS AND METHODS: The cognitive function of 3xTg-AD mice was assessed using the Morris water maze test. The levels of the amyloid beta deposits and NeuN in the hippocampus were evaluated with immunohistochemistry. Brain neurotrophic derived factor (BDNF) and tyrosine kinase B (TrkB) expressions were examined by western blot analysis. RESULTS: LFE treatment significantly ameliorated learning and memory deficits in AD mice, as shown by increased time spent in the target zone during probe tests. In addition, LFE significantly decreased Aß deposits, increased NeuN-positive cells, and upregulated the expression of BDNF and TrkB in the 3xTg AD mice. CONCLUSIONS: The present study suggests that LFE treatment can be a useful strategy for treating memory impairment induced by several neurodegenerative diseases.
