Summary: | 碩士 === 國立陽明大學 === 生物藥學研究所 === 95 === The gut has a complex system to maintain the homeostasis in the battle of limiting inflammatory responses to commensal bacteria while retaining the ability to initiate protective adaptive immune responses to pathogens. Recently, some researches show that intestinal epithelial cells (IECs) may play key role in maintaining the homeostasis, for example, thymic stromal lymphopeitin (TSLP) produced by the IEC is capable of directing dendritic cells towards a Th2 response, and influencing the differentiation properties of monocytes into tissue macrophages. We’d like to develop a system to elucidate the bioactivity of polysaccharides from Chinese herbs (Ganoderma Lucidum, Astragalus mongholicus, Dendrobium huoshanense, Dioscorea opposita) using IEC-6 as a platform, and how they regulate intestinal immune system.
With the treatment of GaLuPS and AsMoPS,IEC-6 can up-regulate IL-6、TNF-α、TLR7、TLR9 gene expression, whileas DeCaPS can up-regulate TGF-刍 gene expression, which is known as immunosuppressive cytokine, leading to the proliferation of regulatory T cell.
In our in vivo OVA-induced asthma animal model, oral treatment with 30 and 90 mg/kg/day DeCaPS was shown to suppress asthma induced by active immunization and challenged with OVA. Here we show that DeCaPS can reduce pulmonary eosinophil recruitment and OVA-specific IgE in serum and bronchoalveolar lavage fluids (BALF), attenuate inflammation in lung, and decrease bronchial hyper-reactivity stimulated by methacholine. We also found that IL-13 and eosinophil-chemokine eotaxin(CCL11) mRNA from lung homogenates are lower in DeCaPS group. Furthermore, the population of CD4+CD25+ increases in intestinal lamina propira with the treatment of DeCaPS, whereas there is no difference in mediastinal lymph node in lung and spleen. According to these results, we demonstrate that DeCaPS has potential to attenuate asthma by suppressing the recruitment of eosinophil and Th2 cell in lung.
Our lab had previously demonstrated that DisPoPS has potential to be used as mucosal adjuvant, so we use BALB/c mice challenged with influenza vaccine mixed with DisPoPS intranasally to confirm this result. After sacrificing the mice at day 30, we found that DisPoPS was capable of inducing a significant increase in HA-specific total IgG and IgA from lung wash、nasal、vaginal wash and serum. Our results showed that DisPoPS is a good mucosal adjuvant.
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