An immunomodulatory protein, Ling Zhi-8, induced activation and maturation of human monocyte-derived dendritic cells by the NF-κB and MAPK pathways

Yu Li Lin, Yu Chih Liang, Yu Shan Tseng, Hsin Yi Huang, Shu Yu Chou, Ruey Shyang Hseu, Ching Tsan Huang, Bor Luen Chiang

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

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, naïve T cell-stimulatory capacity and increased, naïve 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.

Original languageEnglish
Pages (from-to)877-889
Number of pages13
JournalJournal of Leukocyte Biology
Volume86
Issue number4
DOIs
Publication statusPublished - Oct 2009

Fingerprint

Interleukin-10
Dendritic Cells
Monocytes
Interleukin-12
Reishi
HLA-DR Antigens
Interleukin-23
T-Lymphocytes
HEK293 Cells
Agaricales
Endocytosis
Interleukin-8
Antibody Formation
Interleukin-2
Immunization
Fungi
Phosphorylation
Cytokines
Antigens
Ganoderma lucidum LZ-8 protein

Keywords

  • Cytokine
  • Dendritic cells
  • LZ-8
  • Signal transduction
  • T cells

ASJC Scopus subject areas

  • Cell Biology
  • Immunology

Cite this

An immunomodulatory protein, Ling Zhi-8, induced activation and maturation of human monocyte-derived dendritic cells by the NF-κB and MAPK pathways. / Lin, Yu Li; Liang, Yu Chih; Tseng, Yu Shan; Huang, Hsin Yi; Chou, Shu Yu; Hseu, Ruey Shyang; Huang, Ching Tsan; Chiang, Bor Luen.

In: Journal of Leukocyte Biology, Vol. 86, No. 4, 10.2009, p. 877-889.

Research output: Contribution to journalArticle

Lin, Yu Li ; Liang, Yu Chih ; Tseng, Yu Shan ; Huang, Hsin Yi ; Chou, Shu Yu ; Hseu, Ruey Shyang ; Huang, Ching Tsan ; Chiang, Bor Luen. / An immunomodulatory protein, Ling Zhi-8, induced activation and maturation of human monocyte-derived dendritic cells by the NF-κB and MAPK pathways. In: Journal of Leukocyte Biology. 2009 ; Vol. 86, No. 4. pp. 877-889.
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AU - Liang, Yu Chih

AU - Tseng, Yu Shan

AU - Huang, Hsin Yi

AU - Chou, Shu Yu

AU - Hseu, Ruey Shyang

AU - Huang, Ching Tsan

AU - Chiang, Bor Luen

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N2 - 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, naïve T cell-stimulatory capacity and increased, naïve 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.

AB - 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, naïve T cell-stimulatory capacity and increased, naïve 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.

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