JP2008517100A5

JP2008517100A5 -

Info

Publication number: JP2008517100A5
Application number: JP2007536927A
Authority: JP
Filing date: 2005-10-14
Publication date: 2008-11-27

Claims

A fucose-containing glycoprotein fraction of an extract of Ganoderma Lucidum comprising at least one polysaccharide and a glycopeptide having a fucose residue.

The fucose-containing glycoprotein fraction according to claim 1, wherein the fraction contains a saccharide component, and the saccharide component contains a fucose residue bound by an α1,2-fucoside bond.

The fucose-containing glycoprotein fraction according to claim 1, wherein the fraction contains a saccharide component, and the saccharide component contains a terminal fucose residue.

An effective amount of the fucose-containing glycoprotein fraction of an extract of Ganoderma Lucidum (Reishi) containing a glycopeptide having at least one polysaccharide and fucose residues A including methods administering to said cells,
Whether the cell is a mammalian cell, and the method is a method of mediating an immune regulation phenomenon associated with gene expression of IL-1 in a mammalian cell;
Whether the cell is a mammalian cell and the method is a method of stimulating the expression of inflammatory cytokines in a mammalian cell;
Whether the cell is a mammalian cell and the method is a method of modulating a protein kinase pathway associated with interleukin 1 which is an inflammatory cytokine in mammalian cells ;
Whether the cell is a mononuclear cell and the method is a method of regulating the differentiation of a mononuclear cell,
Whether the cell is a NK cell, and the method is a method of increasing NK cell cytotoxicity against NK-sensitive tumor cells;
Whether the cell is a mammalian cell and the method is a method of activating cytokine expression in a mammalian cell;
Whether the cell is mouse spleen B cell or human B cell, and the method is a method of activating Blimp-1 expression in mouse spleen B cell or human B cell,
Whether the cell is a human mature dendritic cell, and the method is a method of activating Blimp-1 expression in a human mature dendritic cell;
Whether the cell is a macrophage and the method inhibits LPS-induced nitric oxide production in macrophages;
The cells are spleen cells and the method is a method of activating spleen cell proliferation, or
A method wherein the cell is a spleen cell and the method is a method of modifying the proteome of a spleen cell.

The method according to claim 4, wherein the immunomodulating phenomenon includes secretion of interleukin 1 and / or a precursor thereof.

6. The method according to claim 5, wherein an effective amount of the fucose-containing glycoprotein fraction is an amount that induces up-regulation of secretion of interleukin 1 and / or its precursor.

6. The method of claim 5, wherein the precursor is pro-IL-1 protein.

The method according to claim 4, wherein the immunoregulatory phenomenon includes expression of interleukin 1 converting enzyme.

9. The method of claim 8, wherein an effective amount of the fucose-containing glycoprotein fraction is an amount that induces up-regulation of interleukin 1 converting enzyme expression.

The method according to claim 4, wherein the cells are human macrophages or mouse macrophages.

The method according to claim 4, wherein the cells are mouse spleen cells.

The method according to claim 4, wherein the inflammatory cytokine is interleukin-1.

An effective amount of the fucose-containing glycoprotein fraction activates PKC, MEK1, PAK and / or MAPKs in a cell, and the amount by which activated PKC, MEK1, PAK and / or MAPKs results in the production of multiple cytokines 5. The method of claim 4, wherein the method stimulates the expression of inflammatory cytokines in mammalian cells.

14. The method of claim 13, wherein the effective amount is an amount that activates the PKC / MEK1 / ERK signaling pathway and activation of the pathway results in transcription, post-transcriptional and post-translational regulation of interleukin 1 gene expression. .

15. The method of claim 14, wherein the control of post-translational regulation of interleukin 1 gene expression comprises activation of interleukin 1 convertase.

15. The method of claim 14, wherein the signaling pathway comprises a PTK → PKC → MEK1 → ERK pathway.

15. The method of claim 14, wherein the signaling pathway comprises a PTK → Rac1 → PAK →→ p38 pathway.

The method according to claim 17, wherein the route is PTK → Rac1 → PAK →→ JNK.

15. The method of claim 14, wherein the pathway is a PI3K signaling pathway.

A method for inducing a TLR-mediated phenomenon in a mammalian cell, said method comprising administering to said cell an effective amount of a fucose-containing glycoprotein fraction of an extract of Ganoderma Lucidum How to induce the phenomenon.

23. The method of claim 22, wherein the TLR mediated phenomenon is the production of inflammatory cytokines.

24. The method of claim 23, wherein the inflammatory cytokine is interleukin-1.

An effective amount of the fucose-containing glycoprotein fraction is CD14 in cell and cell monocyte / macrophage differentiation. ⁺⁺ CD26 ⁺⁺ 6. The method of claim 4, wherein the method modulates mononuclear cell differentiation in an amount that results in increased expression.

An effective amount of the fucose-containing glycoprotein fraction is CD83 in cell and cell dendritic cell differentiation. ⁺⁺ CD1a ⁺⁺ 6. The method of claim 4, wherein the method modulates mononuclear cell differentiation in an amount that results in increased expression.

An effective amount of the fucose-containing glycoprotein fraction is CD16 in cell and cell NK cell differentiation. ⁺⁺ CD56 ⁺⁺ 6. The method of claim 4, wherein the method modulates mononuclear cell differentiation in an amount that results in increased expression.

5. The method of claim 4, wherein an effective amount of the fucose-containing glycoprotein fraction is an amount that results in increased NK cytotoxicity against NK-sensitive tumor cells.

The NK cell is CD3 ⁺⁺ CD56 ⁺⁺ NKT cells or CD3 ^-- CD56 ⁺⁺ The method according to claim 4, wherein the cytotoxicity of NK cells against NK-sensitive tumor cells, which are NK cells, is increased.

Cytokines activate cytokine expression in mammalian cells selected from the group consisting of IL-1, IL6, IL-12, IFN-γ, TNF-α, GM-CSF, G-CSF and M-CSF The method of claim 4.

5. The method of claim 4, wherein an effective amount of the fucose-containing glycoprotein fraction activates Blimp 1 expression in mature human dendritic cells that induces Blimp-1 mRNA in the cell.

A composition comprising an effective amount of a fucose-containing glycoprotein fraction of an extract of Ganoderma Lucidum comprising at least one polysaccharide and a glycopeptide having a fucose residue in a suitable medium, carrier or adjuvant Wherein the composition is
Whether to mediate immune regulation associated with IL-1 gene expression in mammalian cells,
For stimulating the expression of inflammatory cytokines in mammalian cells,
To regulate the protein kinase pathway associated with interleukin 1, an inflammatory cytokine in mammalian cells,
To induce a TLR-mediated phenomenon in mammalian cells,
For regulating the differentiation of mononuclear cells,
To increase NK cell cytotoxicity against NK sensitive tumor cells, or
The above composition, which is for activating the expression of cytokines in mammalian cells.

Claims for mediating immune modulation associated with IL-1 gene expression in mammalian cells, wherein the effective amount of the fucose-containing glycoprotein fraction is an amount that induces up-regulation of secretion of interleukin 1 and / or its precursors Item 30. The composition according to item 30.

31. To mediate immune modulation associated with IL-1 gene expression in mammalian cells, wherein an effective amount of the fucose-containing glycoprotein fraction is an amount that induces upregulation of interleukin 1 convertase expression. Composition.

31. The composition of claim 30, for mediating immune modulation associated with IL-1 gene expression in mammalian cells, wherein the cells are human macrophages, mouse macrophages or mouse spleen cells.

Inflammation in mammalian cells, wherein the effective amount is the amount that activates PKC, MEK1, PAK and / or MAPKs in the cell and the activated PKC, MEK1, PAK and / or MAPKs results in the production of multiple cytokines 31. The composition of claim 30 for modulating a protein kinase pathway associated with interleukin 1, a sex cytokine.

Inflammatory in mammalian cells, wherein the effective amount is an amount that activates the PKC / MEK1 / ERK signaling pathway and activation of the pathway results in transcription, post-transcriptional and post-translational regulation of interleukin 1 gene expression 31. The composition of claim 30, for modulating a protein kinase pathway associated with the cytokine interleukin-1.

31. Regulation of post-translational regulation of interleukin 1 gene expression, including activation of interleukin 1 convertase, for modulating protein kinase pathways associated with inflammatory cytokine interleukin 1 in mammalian cells. The composition as described.

32. The composition of claim 30, for inducing a TLR-mediated phenomenon in a mammalian cell, wherein the TLR-mediated phenomenon is production of interleukin 1 in the cell.

Said effective amount is CD14 in cell and cell monocyte / macrophage differentiation. ⁺⁺ CD26 ⁺⁺ 32. The composition of claim 30, for modulating mononuclear cell differentiation in an amount that results in increased expression.

The effective amount is CD83 in cell and cell dendritic cell differentiation. ⁺⁺ CD1a ⁺⁺ 32. The composition of claim 30, for modulating mononuclear cell differentiation in an amount that results in increased expression.

Said effective amount is CD16 in NK cell differentiation of cells and cells. ⁺⁺ CD56 ⁺⁺ 32. The composition of claim 30, for modulating mononuclear cell differentiation in an amount that results in increased expression.

The NK cell is CD3 ⁺⁺ CD56 ⁺⁺ NKT cells or CD3 ^-- CD56 ⁺⁺ 31. The composition of claim 30 for increasing NK cell cytotoxicity against NK sensitive tumor cells, which are NK cells.