Respiratory syncytial virus persistent infection causes acquired CFTR dysfunction in human bronchial epithelial cells / 中南大学学报(医学版)

Objective: Many studies have shown that respiratory syncytial virus persistent infection may be the main cause of chronic respiratory pathology. However, the mechanism is unclear. Cystic fibrosis transmembrane conduction regulator (CFTR) is an apical membrane chloride channel, which is very important for the regulation of epithelial fluid, chloride ion, and bicarbonate transport. CFTR dysfunction will lead to changes in bronchial secretions and impair mucus clearance, which is related to airway inflammation. In our previous study, we observed the down-regulation of CFTR in airway epithelial cells in respiratory syncytial virus (RSV) infected mouse model. In this study, we further investigated the expression and function of CFTR by constructing an airway epithelial cell model of RSV persistent infection. Methods: 16HBE14o- cells were infected with RSV at 0.01 multiplicity of infection (MOI). The expression of CFTR was detected by real-time RT-PCR, immunofluorescence, and Western blotting. The intracellular chloride concentration was measured by N-(ethoxycarbonylmethyl)-6-methoxyquinolium bromide (MQAE) and the chloride current was measured by whole-cell patch clamp recording. Results:16HBE14o-cells infected with RSV were survived to successive passages of the third generation (G3), while the expression and function of CFTR was progressively decreased upon RSV infection from the first generation (G1) to G3. Exposure of 16HBE14o-cells to RSV led to the gradual increase of TGF-β1 as well as phosphorylation of Smad2 following progressive RSV infection. Disruption of TGF-β1 signaling by SB431542 prevented Smad2 phosphorylation and rescued the expression of CFTR. Conclusion:RSV infection can lead to defective CFTR function in airway epithelial cells, which may be mediated via activation of TGF-β1 signaling pathway.

Involvement of epigenetic modification in epithelial immune responses during respiratory syncytial virus infection.

The epithelial cells of bronchi (BECs) act as a protective wall against potential pathogens and foreign particles that controls many aspects of respiratory immune response. The BECs act as not only a physical protecting wall of the airways but also as a significant part of both the innate and adaptive immune responses. Many kind of epithelium-associated communicating pathways which are triggered by genetic and environmental causating agents get involved in development of respiratory tract abnormalities. Epigenetic dysregulation is one potential mechanism which may mediate between adverse in early life exposures such as severe infections and immunological function deficits in later life. Epigenetic factors which regulate the respiratory tract lining structure and role are also an attractive area to assess the susceptibility of respiratory tract diseases. Several studies show that the key genes in epithelium-related signaling pathways have epigenetic modifications. The interactions mediating the relationship between severe bronchiolitis caused by RSV and their adverse consequences in childhood are broadly understood as immunological in nature, however, are yet to be fully uncovered. Thus, our study explained the immune action of epithelium and RSV-triggered immune imbalance of epithelium through epigenetic modifications in the mechanism of airway hyperresponsiveness.

Searching of experiment innovation in medical functional experimental teaching / 中华医学教育探索杂志

To improve students' experimental research skills,innovative consciousness,promote the construction of functional experimental center,we established series of “comprehensive,contrivable,innovative” experiments in medical students.

The effect of intermittent hypoxia on bodyweight, serum glucose and cholesterol in obesity mice.

This article tests mice's indicators of body nutritional metabolism under tolerable hypoxic conditions, in order to explore the effects of moderate intermittent hypoxia on the bodyweight, blood sugar and blood cholesterol of obese mice and to identify the role of leptin in these effects; this study applies high-fat diet to establish Mice Obesity Models and observes the intervention effects of intermittent hypoxic training in this Model. Small healthy mice are classified in 4 groups at random, that is, Group A (Normal), Group B (Normal Hypoxia) fed with normal foods and undergoing Intermittent Hypoxic Training (IHT), Group C (Fatty-diet) fed with High-Fat and High-Sugar (HFHS) foods without IHT and Group D (Fatty-diet and Hypoxia) fed with HFHS foods with IHT. After 40 days of feeding and hypoxic training, weigh the mice, measure the levels of blood sugar and blood cholesterol with a full automatic biochemical analyzer, measure serum leptin concentration by enzyme-linked immunosorbent assay (ELISA) technique, inspect liver leptin receptor expression and liver fat slice by immunohistochemistry. It is found that compared to control group, after experiment, the average bodyweight, blood sugar, blood cholesterol and serum leptin concentration in Group C is increased significantly and numerous fat cells are distributed in the liver, which indicates that hyperlipemia model has been successfully established; after intermittent hypoxic training, the average bodyweight, blood sugar, blood cholesterol and liver fat cells distribution density and scope in Group B and D are lower than those in Group A and C, while serum leptin concentration is increased significantly; liver leptin receptor expression in Group D is higher than that in Group C. And hypoxia groups have no trauma conclusion. Moderate intermittent hypoxia can reduce bodyweight by increasing leptin concentration and enhancing liver leptin expression and it can also reduce the level of blood sugar and blood cholesterol and meanwhile prevent steatosis in liver cells effectively.

Promoting experimental center opening with research teaching / 中华医学教育探索杂志

To exert the role of high quality resources of national experimental teaching demonstration center in teaching,we have promoted laboratory opening through research teaching.By the contest of university students’experiment designing and inviting public bidding for exploring experiment,we encourage students to conduct innovation research,blazed their orexis and enthusiasm to start scientific research.We also encourage teachers to explore new teaching methods and innovated experimental items.