Poria cocos Immunomodulatory Protein Induces TH1 Immune Response by Activated Dendritic Cells

Autor: Po-Yu Chi, 紀柏羽
Rok vydání: 2014
Druh dokumentu: 學位論文 ; thesis
Popis: 102
Poria cocos protein (PCP), which is purified from dried sclerotium of Poria cocos, is a 35.6 kDa heterodimer protein including 14.3 and 21.3 kDa glycosyl subunits. In our previous results, PCP could active RAW264.7 cells and mouse peritoneal macrophages. This protein could also up-regulate murine T cells to secrete IFN-γ in the presence of anti-CD3/CD28 mAbs and inhibit TH2 immune-response in patch test for atopic dermatitis. However, PCP could not directly activate the differentiation of CD90.2+ T cells to TH1 cells, suggesting antigen-presenting cells as dendritic cells (DCs) could be responsible for the activation of PCP on TH1 cells. In this study, we first found that PCP could up-regulate the expression of CD40, CD80, and CD86 and induce secretion of IL-6 and IL-12p70 on murine DCs. In the results of PCP incubated with DCs of TLR2-/- and TLR4-/- mice, we found that PCP might induce DCs activation through neither TLR2 nor TLR4 pathway. Second, PCP significantly increased the antigen-presentimg ability of murine DCs to promote cell proliferation and IFN-γ secretion of OVA-specific DO11.10 CD90.2+ T cells. Meanwhile, these DCs could inhibit the OVA-specific IL-4 secretion by DO11.10 CD90.2+ T cells. According to the results, we suggested that PCP can help DCs presenting antigen and skewing immune-response to TH1. Finally, in OVA-induced asthma mouse model, oral administration of PCP (100 μg/day) could increase the production of IFN-γ in bronchoalveolar lavage fluid (BALF) and OVA-specific IgG2a in serum. Oral administration of PCP could also down-regulate the amount of eosinophils and TH2 cytokines (IL-4, IL-5, and IL-13) in BALF, OVA-specific IgE in serum, and cell infiltration in mouse lung sections. In conclusion, PCP can activate DCs to promote differentiation of TH1 cells and suppress TH2 immune-response in mouse model of asthma.
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