https://scholars.lib.ntu.edu.tw/handle/123456789/567908
標題: | An immunomodulatory protein, Ling Zhi-8, induced activation and maturation of human monocyte-derived dendritic cells by the NF-κB and MAPK pathways | 作者: | Lin Y.-L. Liang Y.-C. Tseng Y.-S. Huang H.-Y. Chou S.-Y. Hseu R.-S. Huang C.-T. BOR-LUEN CHIANG |
關鍵字: | Cytokine; Dendritic cells; LZ-8; Signal transduction; T cells | 公開日期: | 2009 | 卷: | 86 | 期: | 4 | 起(迄)頁: | 877-889 | 來源出版物: | Journal of Leukocyte Biology | 摘要: | Ganoderma lucidum, an oriental medicinal mushroom, has been widely used in Asia to promote health and longevity. LZ-8 is a protein derived from the fungus G. lucidum and has immunomodulatory capacities. In this study, we investigated the immune modulatory effects of rLZ-8 on human monocyte-derived DCs. Treatment of DC with rLZ-8 resulted in the enhanced cell-surface expression of CD80, CD86, CD83, and HLA-DR, as well as the enhanced production of IL-12 p40, IL-10, and IL-23, and the capacity for endocytosis was suppressed in DCs. In addition, treatment of DCs with rLZ-8 resulted in an enhanced, na?ve T cell-stimulatory capacity and increased, na?ve T cell secretion of IFN-γ and IL-10. Neutralization with antibodies against TLR4 inhibited the rLZ-8-induced production of IL-12 p40 and IL-10 in DCs. rLZ-8 can stimulate TLR4 or TLR4/MD2-transfected HEK293 cells to produce IL-8. These results suggested an important role for TLR4 in signaling DCs upon incubation with rLZ-8. Further study showed that rLZ-8 was able to augment IKK, NF-κB activity, and also IκBα and MAPK phosphorylation. Further, inhibition of NF-κB by helenalin prevented the effects of rLZ-8 in the expression of CD80, CD86, CD83, and HLA-DR and production of IL-12 p40 and IL-10 in various degrees. To confirm the in vitro data, we investigated the effect of rLZ-8 further on antigen-specific antibody and cytokine production in BALB/c mice. Immunization with OVA/ rLZ-8 showed that the anti-OVA IgG2a, IFN-γ, and IL-2 were increased significantly compared with OVA alone in BALB/c mice. In conclusion, our experiments demonstrated that rLZ-8 can effectively promote the activation and maturation of immature DCs, preferring a Th1 response, suggesting that rLZ-8 may possess a potential effect in regulating immune responses. ? Society for Leukocyte Biology. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-70349184084&doi=10.1189%2fjlb.0708441&partnerID=40&md5=abd7af684ad14840aeb1348703659ad6 https://scholars.lib.ntu.edu.tw/handle/123456789/567908 |
ISSN: | 0741-5400 | DOI: | 10.1189/jlb.0708441 | SDG/關鍵字: | B7 antigen; CD83 antigen; CD86 antigen; fungal protein; gamma interferon; helenalin; HLA DR antigen; immunoglobulin enhancer binding protein; immunoglobulin G2a; interleukin 10; interleukin 12; interleukin 23; ling zhi 8 protein; mitogen activated protein kinase; neutralizing antibody; protein p40; toll like receptor 4; unclassified drug; animal experiment; antigen specificity; article; Bagg albino mouse; cell maturation; cell strain HEK293; cell surface; cytokine production; dendritic cell; endocytosis; enzyme phosphorylation; female; human; human cell; immune response; immunization; immunomodulation; in vitro study; incubation time; lymphocyte activation; monocyte; mouse; nonhuman; priority journal; signal transduction; Th1 cell; Animals; Antigens, CD; Cytokines; Dendritic Cells; Fungal Proteins; Gene Expression Regulation; HLA-DR Antigens; Humans; Immunoglobulin G; Immunologic Factors; MAP Kinase Signaling System; Mice; Mice, Inbred BALB C; Monocytes; NF-kappa B; Reishi; Th1 Cells; Toll-Like Receptor 4; Basidiomycota; Fungi; Ganoderma lucidum; Mus |
顯示於: | 醫學系 |
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