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The effects of epigallocatechin-3-gallate (EGCG) on dendritic cells (DC) maturation were investigated. EGCG, in a dose-dependent manner, profoundly inhibited CD80, CD86, and MHC class I and II expression on bone marrow-derived murine myeloid DC. EGCG restored the decreased dextran-FITC uptake and inhibited enhanced IL-12 production by LPS-treated DC. EGCG-treated DC were poor stimulators of nai;ve allogeneic T-cell proliferation and reduced levels of IL-2 production in responding T cells. EGCG-pretreated DC inhibited LPS-induced MAPKs, such as ERK1/2, p38, JNK, and NF-kappaB p65 translocation. Therefore, the molecular mechanisms by which EGCG antagonized LPS-induced DC maturation appeared to involve the inhibition of MAPK and NF-kappaB activation. These novel findings provide new insight into the immunopharmacological role of EGCG and suggest a novel approach to the manipulation of DC for therapeutic application of autoimmune and allergic diseases.

Acidic polysaccharides (PL) isolated from Phellinus linteus are known to stimulate the proliferation of T lymphocytes and humoral immune functions to act as a polyclonal activator of B cells, and to inhibit tumor growth and metastasis. However, little is known about their immunomodulating effects or the effects of its mechanisms on murine bone marrow (BM)-derived dendritic cells (DC). In this study, it profoundly increased CD80, CD86, MHC I, and MHC II expression in murine, GM-CSF and IL-4 stimulated, BM-derived myeloid DC. The ability of unstimulated DC to uptake dextran was higher than that of PL- or LPS-stimulated DC. We analyzed the concentration of IL-12 secreted by DC using flow cytometry and ELISA. Untreated DC secreted a low concentration of IL-12, while PL- or LPS-stimulated DC secreted higher levels of IL-12 than untreated DC. There were no remarkable differences in the concentrations of IL-12 produced by PL- or LPS-stimulated DC. However, polymyxin B (PB; an LPS inhibitor) effectively inhibited the surface molecules and IL-12 production induced by LPS, but had no effect on the PL in DC. PL-treated DC were much more potent antigen-presenting cells in allogeneic immune response than untreated DC. PL treatment not only formed morphologically mature DC but also induced predominant migration to lymphoid tissues. Moreover, the inhibitors of protein tyrosine kinase (PTK) or protein kinase C (PKC) significantly blocked the expression of surface molecules and IL-12 production in PL-stimulated DC. Treatment of DC with PL directly induced PKC activity and phosphorylated PTK. Furthermore, CD11b and/or CD18 partially mediated PL-induced DC maturation.

Mushroom polysaccharides are increasingly being utilized to treat a wide variety of diseases. Aqueous extracts from the Phellinus linteus have been reported to have anti-tumor and immunomodulatory properties. In particular, acidic polysaccharide (PL) isolated from P. linteus induced a secretory and cellular macrophage response. However, the exact mechanism by which PL regulates the macrophage functions remains unclear. PL-treated murine peritoneal macrophages in vitro and in vivo dramatically induced the production of NO. PL enhanced the lytic death of B16 cells through the production of NO. The present study examined signal molecules that may participate in PL-elicited responses by macrophages. The data demonstrated that a protein kinase C (PKC) inhibitor, staurosporine, and a protein tyrosine kinase (PTK) inhibitor, genistein, inhibited the tumoricidal activity of macrophages induced by PL. In addition, these inhibitors blocked the production of NO and the expression of surface molecules in PL-stimulated macrophages. Furthermore, CD11b/CD18 possibly mediates PL-induced cell activation. These results suggest that PL stimulates NO production for tumoricidal activity and induces cell-mediated immunity by increasing surface molecules, and the process may be a mechanism by which PL produces its therapeutic effects.