Immunomodulatory -Glucan from Lentinus edodes Activates Mitogen-activated Protein Kinases and Nuclear Factor- B in Murine RAW 264.7 Macrophages

Department of Chemistry, Wuhan University, Wuhan 430072, China.
Journal of Biological Chemistry (Impact Factor: 4.57). 07/2011; 286(36):31194-8. DOI: 10.1074/jbc.M111.246470
Source: PubMed


Lentinan, a cell wall β-glucan from the fruiting bodies of Lentinus edodes, is well known to be a biological defense modifier, but the signal transduction pathway(s) induced by Lentinan have not been elucidated. In this study, we extracted Lentinan (LNT-S) by ultrasonication from Lentinus edodes and report that, in murine RAW 264.7 macrophages, LNT-S glucan activated NF-κB p65 and triggered its nuclear translocation as determined by Western blotting. Moreover, LNT-S enhanced NF-κB-luciferase activity in the Dual-Luciferase gene system assay. Its upstream signaling molecules, MAPKs such as ERK1/2 and JNK1/2, were shown to be activated by assessing the level of phosphorylation in a time- and concentration-dependent manner, but its downstream proinflammatory enzyme, inducible NOS, was not observed. The data evaluated using a TNF-α ELISA kit and Griess reagent further demonstrated that no proinflammatory mediators such as TNF-α and NO were produced by LNT-S stimulation in RAW 264.7 cells. In contrast, LPS significantly induced inducible NOS expression and increased NO and TNF-α production, which are associated with activation of the NF-κB p65/p50 heterodimer complex. It is possible that LNT-S did not activate NF-κB p65/p50, and the activation of NF-κB p65 was not sufficient to stimulate cytokine production. These data demonstrate that LNT-S glucan carries out its immunomodulating activity by activating MAPK signaling pathways without secretion of TNF-α and NO.

Download full-text


Available from: Pan Chen, Feb 12, 2014
  • Source
    • "BioMed Research International tissues, inhibit T-cell differentiation and functions, lower cytotoxic T-cell function, induce T-cell apoptosis, secrete CCL18, and attract na¨ıve T cell [10] [16] [32] [35]. Immune modulatory and antitumor effects of mushroom beta-glucan have been noted by Ikekawa et al. in 1968 in the fruiting body extracts of Lentinus edodes, Coriolus versicolor, Ganoderma tsugae, Flammulina velutipes, and Tricholoma matsutake which have demonstrated significant antitumor activities towards transplanted tumor cells of sarcoma 180 [36] [37] [38]. Celecoxib is a COX-2 inhibitor and inhibits tumor growth by inhibiting synthesis of prostaglandin [39] [40] [41] [42] [43] [44] [45] [46]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The present study showed that oral mushroom beta-glucan treatment significantly increased IFN-γ mRNA expression but significantly reduced COX-2 mRNA expression within the lung. For LLC tumor model, oral Ganoderma lucidum or Antrodia camphorata polysaccharides treatments significantly reduced TGF-β production in serum. In addition, IL-12 and IFN-γ mRNA expression were significantly increased, but IL-6, IL-10, COX-2, and TGF-β mRNA expression were substantially following oral mushroom polysaccharides treatments. The study highlights the efficacious effect of mushroom polysaccharides for ameliorating the immune suppression in the tumor microenvironment. Increased M1 phenotype of tumor-associated macrophages and attenuated M2 phenotype of tumor-associated macrophages could be achieved by ingesting mushroom polysaccharides.
    07/2015; 2015:604385. DOI:10.1155/2015/604385
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Lentinan (LNT), a β-glucan from the fruiting bodies of Lentinus edodes, is well known to have immunomodulatory activity. NO and TNF-α are associated with many inflammatory diseases. In this study, we investigated the effects of LNT extracted by sonication (LNT-S) on the NO and TNF-α production in LPS-stimulated murine RAW 264.7 macrophages. The results suggested that treatment with LNT-S not only resulted in the striking inhibition of TNF-α and NO production in LPS-activated macrophage RAW 264.7 cells, but also the protein expression of inducible NOS (iNOS) and the gene expression of iNOS mRNA and TNF-α mRNA. It is surprising that LNT-S enhanced LPS-induced NF-κB p65 nuclear translocation and NF-κB luciferase activity, but severely inhibited the phosphorylation of JNK1/2 and ERK1/2. The neutralizing antibodies of anti-Dectin-1 and anti-TLR2 hardly affected the inhibition of NO production. All of these results suggested that the suppression of LPS-induced NO and TNF-α production was at least partially attributable to the inhibition of JNK1/2 and ERK1/2 activation. This work discovered a promising molecule to control the diseases associated with overproduction of NO and TNF-α.
    Journal of Biological Chemistry 11/2011; 287(2):871-8. DOI:10.1074/jbc.M111.297887 · 4.57 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Imbalance or malfunction of the immune systems is associated with a range of chronic diseases including autoimmune diseases, allergies, cancers and others. Various innate and adaptive immune cells that are integrated in this complex networking system may represent promising targets for developing immunotherapeutics for treating specific immune diseases. A spectrum of phytochemicals have been isolated, characterized and modified for development and use as prevention or treatment of human diseases. Many cytotoxic drugs and antibiotics have been developed from phytocompounds, but the application of traditional or new medicinal plants for use as immunomodulators in treating immune diseases is still relatively limited. In this review, a selected group of medicinal herbs, their derived crude or fractionated phytoextracts and the specific phytochemicals/phytocompounds isolated from them, as well as categorized phytocompound groups with specific chemical structures are discussed in terms of their immunomodulatory bioactivities. We also assess their potential for future development as immunomodulatory or inflammation-regulatory therapeutics or agents. New experimental approaches for evaluating the immunomodulatory activities of candidate phytomedicines are also discussed.
    Advances in Botanical Research, Edited by Lie-Fen Shyur and Allan S.Y. Lau, 01/2012: pages 197-272; Academic Press.
Show more