Dendritic Cell Activation by Glucan Isolated from Umbilicaria Esculenta
2
조회
0
다운로드
4
인용
0
참고문헌
키워드
초록
Background: Lichen-derived glucans have been known to stimulate the functions of immune cells. However, immunostimulatory activity of glucan obtained from edible lichen, Umbilicaria esculenta, has not been reported. Thus we evaluated the phenotype and functional maturation of dendritic cells (DCs) following treatment of extracted glucan (PUE). Methods: The phenotypic and functional maturation of PUE-treated DCs was assessed by flow cytometric analysis and cytokine production, respectively. PUE-treated DCs was also used for mixed leukocyte reaction to evaluate T cell-priming capacity. Finally we detected the activation of MAPK and NF-κB by immunoblot. Results: Phenotypic maturation of DCs was shown by the elevated expressions of CD40, CD80, CD86, and MHC class I/II molecules. Functional activation of DCs was proved by increased cytokine production of IL-12, IL-1β, TNF-α, and IFN-α/β, decreased endocytosis, and enhanced proliferation of allogenic T cells. Polymyxin B, specific inhibitor of lipopolysaccharide (LPS), did not affect PUE activity, which suggested that PUE was free of LPS contamination. As a mechanism of action, PUE increased phosphorylation of ERK, JNK, and p38 MAPKs, and enhanced nuclear translocation of NF-κB p50/p65 in DCs. Conclusion: These results indicate that PUE induced DC maturation via MAPK and NF-κB signaling pathways.
Abstract
Background: Lichen-derived glucans have been known to stimulate the functions of immune cells. However, immunostimulatory activity of glucan obtained from edible lichen, Umbilicaria esculenta, has not been reported. Thus we evaluated the phenotype and functional maturation of dendritic cells (DCs) following treatment of extracted glucan (PUE). Methods: The phenotypic and functional maturation of PUE-treated DCs was assessed by flow cytometric analysis and cytokine production, respectively. PUE-treated DCs was also used for mixed leukocyte reaction to evaluate T cell-priming capacity. Finally we detected the activation of MAPK and NF-κB by immunoblot. Results: Phenotypic maturation of DCs was shown by the elevated expressions of CD40, CD80, CD86, and MHC class I/II molecules. Functional activation of DCs was proved by increased cytokine production of IL-12, IL-1β, TNF-α, and IFN-α/β, decreased endocytosis, and enhanced proliferation of allogenic T cells. Polymyxin B, specific inhibitor of lipopolysaccharide (LPS), did not affect PUE activity, which suggested that PUE was free of LPS contamination. As a mechanism of action, PUE increased phosphorylation of ERK, JNK, and p38 MAPKs, and enhanced nuclear translocation of NF-κB p50/p65 in DCs. Conclusion: These results indicate that PUE induced DC maturation via MAPK and NF-κB signaling pathways.
참고문헌 (37)
- Schepetkin IA, "Botanical polysaccharides: macrophage immunomodulation and therapeutic potential", Int Immunopharmacol, 6, pp.317~333 (2006)
- Tzianabos AO, "Polysaccharide immunomodulators as therapeutic agents: structural aspects and biologic function", Clin Microbiol Rev, 13, pp.523~533 (2000)
- Wasser SP, "Medicinal mushrooms as a source of antitumor and immunomodulating polysaccharides", Appl Microbiol Biotechnol, 60, pp.258~274 (2002)
- Nakano H, "A multi-institutional prospective study of lentinan in advanced gastric cancer patients with unresectable and recurrent diseases: effect on prolongation of survival and improvement of quality of life", Hepatogastroenterology, 46, pp.2662~2668 (1999), Kanagawa Lentinan Research Group
- Okamura K, "Clinical evaluation of schizophyllan combined with irradiation in patients with cervical cancer", Cancer, 58, pp.865~872 (1986)
- Pang ZJ, "A protein-bound polysaccharide synergistic with lipopolysaccharide induces nitric oxide release and antioxidant enzyme activities in mouse peritoneal macrophages", Am J Chin Med, 26, pp.133~141 (1998)
- Okazaki M, "Structure-activity relationship of (1-->3)-beta-D-glucans in the induction of cytokine production from macrophages, in vitro", Biol Pharm Bull, 18, pp.1320~1327 (1995)
- Borchers AT, "Mushrooms, tumors, and immunity", Proc Soc Exp Biol Med, 221, pp.281~293 (1999)
- Ingolfsdottir K, "Immunologically active polysaccharide from Cetraria islandica", Planta Med, 60, pp.527~531 (1994)
- Freysdottir J, "In vitro and in vivo immunomodulating effects of traditionally prepared extract and purified compounds from Cetraria islandica", Int Immunopharmacol, 8, pp.423~430 (2008)
- Olafsdottir ES, "Immunologically active (1-->3)-(1-->4)-alpha- D-glucan from Cetraria islandica", Phytomedicine, 6, pp.33~39 (1999)
- Omarsdottir S, "Immunomodulating polysaccharides from the lichen Thamnolia vermicularis var. subuliformis", Phytomedicine, 14, pp.179~184 (2007)
- Olafsdottir ES, "Immunologically active O6-branched (1--＞3)-beta-glucan from the lichen Thamnolia vermicularis var. subuliformis", Phytomedicine, 10, pp.318~324 (2003)
- Kim MS, "Antithrombotic activity of methanolic extract of Umbilicaria esculenta", J Ethnopharmacol, 105, pp.342~345 (2006)
- Kim MS, "Melanogenesis inhibitory effects of methanolic extracts of Umbilicaria esculenta and Usnea longissima", J Microbiol, 45, pp.578~582 (2007)
- Lee KA, "Glucosidase inhibitor from Umbilicaria esculenta", Can J Microbiol, 46, pp.1077~1081 (2000)
- Kim HS, "Induction of dendritic cell maturation by β-glucan isolated from Sparassis crispa", Int Immunopharmacol, 10, pp.1284~1294 (2010)
- Kim JY, "Inhibition of bone marrow-derived dendritic cell maturation by glabridin", Int Immunopharmacol, 10, pp.1185~1193 (2010)
- Kim JY, "Angelan isolated from Angelica gigas Nakai induces dendritic cell maturation through toll-like receptor 4", Int Immunopharmacol, 7, pp.78~87 (2007)
- Kim HS, "Cordlan polysaccharide isolated from mushroom Cordyceps militaris induces dendritic cell maturation through toll-like receptor 4 signalings", Food Chem Toxicol, 48, pp.1926~1933 (2010)
- Banchereau J, "Immunobiology of dendritic cells", Annu Rev Immunol, 18, pp.767~811 (2000)
- Bennaceur K, "Dendritic cells dysfunction in tumour environment", Cancer Lett, 272, pp.186~196 (2008)
- Bennaceur K, "Immunosuppressive networks in the tumour environment and their effect in dendritic cells", Biochim Biophys Acta, 1795, pp.16~24 (2009)
- Harding FA, "CD28-mediated signalling co-stimulates murine T cells and prevents induction of anergy in T-cell clones", Nature, 356, pp.607~609 (1992)
- Gabrilovich DI, "Dendritic cells in antitumor immune responses. II. Dendritic cells grown from bone marrow precursors, but not mature DC from tumor-bearing mice, are effective antigen carriers in the therapy of established tumors", Cell Immunol, 170, pp.111~119 (1996)
- Kusmartsev S, "Effect of tumor-derived cytokines and growth factors on differentiation and immune suppressive features of myeloid cells in cancer", Cancer Metastasis Rev, 25, pp.323~331 (2006)
- Menetrier-Caux C, "Inhibition of the differentiation of dendritic cells from CD34(+) progenitors by tumor cells: role of interleukin-6 and macrophage colony-stimulating factor", Blood, 92, pp.4778~4791 (1998)
- Nefedova Y, "Hyperactivation of STAT3 is involved in abnormal differentiation of dendritic cells in cancer", J Immunol, 172, pp.464~474 (2004)
- Rabinovich GA, "Immunosuppressive strategies that are mediated by tumor cells", Annu Rev Immunol, 25, pp.267~296 (2007)
- Shurin GV, "Neuroblastoma-derived gangliosides inhibit dendritic cell generation and function", Cancer Res, 61, pp.363~369 (2001)
- Kanazawa M, "Effect of PSK on the maturation of dendritic cells derived from human peripheral blood monocytes", Immunol Lett, 91, pp.229~238 (2004)
- Kim GY, "Proteoglycan isolated from Phellinus linteus induces toll- like receptors 2- and 4-mediated maturation of murine dendritic cells via activation of ERK, p38, and NF-kappaB", Biol Pharm Bull, 27, pp.1656~1662 (2004)
- Kim GY, "Effect of water-soluble proteoglycan isolated from Agaricus blazei on the maturation of murine bone marrow-derived dendritic cells", Int Immunopharmacol, 5, pp.1523~1532 (2005)
- Kim R, "Cancer immunosuppression and autoimmune disease: beyond immunosuppressive networks for tumour immunity", Immunology, 119, pp.254~264 (2006)
- Grewal IS, "The role of CD40 ligand in costimulation and T-cell activation", Immunol Rev, 153, pp.85~106 (1996)
- Gately MK, "The interleukin-12", interleukin-12-receptor system: role in normal and pathologic immune responses, 1998, pp.16, 495~521
- Iwasaki A, "Mucosal dendritic cells", Annu Rev Immunol, 25, pp.381~418 (2007)