Oral delivery of allergen protein and gene for the treatment of murine model of asthma

• Main Authors: Shiau-Fang Hung, 洪小芳
• Other Authors: Bor-Luen Chiang
• Format: Others
• Language: zh-TW
• Published: 2002
• Online Access: http://ndltd.ncl.edu.tw/handle/50264315217788191590

碩士 === 國立臺灣大學 === 免疫學研究所 === 90 === Abstract The incidence and severity of asthma is increasing worldwide. Allergic asthma is a chronic airway inflammation disease and associated with activation and involvement of type 2 T helper cells 、eosinophils、mast cells and epithelial cells. These activated cells could release some mediators such as IL-4，IL-5 and histamine which are able to induce the inflammation, airway hyper responsiveness, mucus secretion and subsequently in airway obstruction. Oral tolerance is a state of non- responsiveness to an antigen that is administrated by oral route. Oral tolerance has been used in many animal models to delay development of certain diseases such as Th1-mediated experimental autoimmune encephalomyelitis (EAE) and Th2-induced allergic airway inflammation. In our study, we like to examine the effect and the possible mechanisms of feeding OVA protein and OVA plasmid on animal model of asthma. OVA plasmid mixed with chitosan that is polysaccharides and derived from chitin was delivered to the sensitized mice. Chitosan has positive charges under acidic condition，high biocompatible and non-toxic. It suits to be a gene carrier. The data demonstrated that chitosan can carry the gene into COS-1 cells and the gene expression can be detected. We could also detect the mRNA expression of OVA plasmid in Peyer’s patches, but the level of protein expression is very low. In vivo study showed feeding OVA protein, oral tolerance could be induced in immunized mice and Th2 allergic immune response, OVA-specific IgE、IgG1、airway hyper responsiveness and infiltration of eosinophilis into lung were decreased. However, the mice feed OVA plasmid cannot induce oral tolerance to inhibit the Th2 allergic immune response. The results showed that oral tolerance induced by OVA protein was dose dependent. It is speculated that feeding OVA plasmid cannot induce oral tolerance in immunized mice might be due to the level of protein expression from OVA plasmid is too low in vivo. Furthermore, feeding OVA plasmid along with cytokine plasmids also did not enhance the effect of oral tolerance. In summary, chitosan migh be a good tool to deliver the gene to mucosal immune system. In the future, study on the mechanism of inducing oral tolerance by feeding OVA protein might be important for novel therapeutic approach.