Abstract
Sparassis crispa (SC) is an edible mushroom that harbours β-glucans reported to possess immunostimulatory and anticancer properties. The role of SC in regulating the functional activation of macrophages is yet to be fully elucidated. The objective of this study was to investigate the molecular mechanism underlying the immune-stimulatory function of Sparassis crispa soluble β-glucan (Sc-SG) on macrophages. According to this study, Sc-SG was able to stimulate nitric oxide (NO) production as well as enhance the expression of inducible NO synthase (iNOS) from macrophage-like RAW264.7 cells. NO production was strongly suppressed by mitogen-activated protein kinase (MAPK) inhibitors such as U0126, extracellular signal-regulated kinase, SB203580, a p38 inhibitor, and SP600125, a c-Jun N-terminal kinase inhibitor. Thus, indicating that Sc-SG-induced NO release is possibly mediated by MAPK. Sc-SG induced phosphorylation of extracellular signal-regulated kinase, p38, and JNK in a time-dependent manner. Moreover, Sc-SG triggered the phosphorylation and translocation of c-Jun and c-Fos, components of the transcription factor AP-1, activated by MAPK. The results of this study suggest that MAPK may be a major signaling enzyme that regulates the Sc-SG-mediated NO production in macrophages.
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Bresnihan, B., Pathogenesis of joint damage in rheumatoid arthritis. J. Rheumatol., 26, 717–719 (1999).
Burmester, G. R., Stuhlmuller, B., Keyszer, G., and Kinne, R. W., Mononuclear phagocytes and rheumatoid synovitis. Mastermind or workhorse in arthritis? Arthritis Rheum., 40, 5–18 (1997).
Byeon, S. E., Chung, J. Y., Lee, Y. G., Kim, B. H., Kim, K. H., and Cho, J. Y., In vitro and in vivo anti-inflammatory effects of taheebo, a water extract from the inner bark of Tabebuia avellanedae. J. Ethnopharmacol., 119, 145–152 (2008).
Cho, E. J., Oh, J. Y., Chang, H. Y., and Yun, J. W., Production of exopolysaccharides by submerged mycelial culture of a mushroom Tremella fuciformis. J. Biotechnol., 127, 129–140 (2006).
Cho, J. Y., Baik, K. U., Jung, J. H., and Park, M. H., In vitro anti-inflammatory effects of cynaropicrin, a sesquiterpene lactone, from Saussurea lappa. Eur. J. Pharmacol., 398, 399–407 (2000).
Choi, J. J., Jin, M., Lee, J. K., Lee, W. Y., Park, Y. I., Han, Y. N., and Kim, S., Control of cytokine gene expression by PG101, a water-soluble extract prepared from Lentinus lepideus. Biochem. Biophys. Res. Commun., 339, 880–887 (2006).
Denkers, E. Y., Butcher, B. A., Del Rio, L., and Kim, L., Manipulation of mitogen-activated protein kinase/nuclear factor-kappaB-signaling cascades during intracellular Toxoplasma gondii infection. Immunol. Rev., 201, 191–205 (2004).
Espinoza, B., Silman, I., Arnon, R., and Tarrab-Hazdai, R., Phosphatidylinositol-specific phospholipase C induces biosynthesis of acetylcholinesterase via diacylglycerol in Schistosoma mansoni. Eur. J. Biochem., 195, 863–870 (1991).
Gracie, J. A., Forsey, R. J., Chan, W. L., Gilmour, A., Leung, B. P., Greer, M. R., Kennedy, K., Carter, R., Wei, X. Q., Xu, D., Field, M., Foulis, A., Liew, F. Y., and McInnes, I. B., A proinflammatory role for IL-18 in rheumatoid arthritis. J. Clin. Invest., 104, 1393–1401 (1999).
Harada, T., Miura, N. N., Adachi, Y., Nakajima, M., Yadomae, T., and Ohno, N., IFN-gamma induction by SCG, 1,3-beta-D-glucan from Sparassis crispa, in DBA/2 mice in vitro. J. Interferon Cytokine Res., 22, 1227–1239 (2002).
Harada, T., Masuda, S., Arii, M., Adachi, Y., Nakajima, M., Yadomae, T., and Ohno, N., Soy isoflavone aglycone modulates a hematopoietic response in combination with soluble beta-glucan: SCG. Biol. Pharm. Bull., 28, 2342–2345 (2005).
Harada, T. and Ohno, N., Contribution of dectin-1 and granulocyte macrophage-colony stimulating factor (GM-CSF) to immunomodulating actions of beta-glucan. Int. Immunopharmacol., 8, 556–566 (2008).
Indar, A. A. and Maxwell-Armstrong, C. A., Active specific immunotherapy for colorectal cancer. Expert Rev. Anticancer Ther., 3, 685–694 (2003).
Jeong, Y. T., Yang, B. K., Jeong, S. C., Kim, S. M., and Song, C. H., Ganoderma applanatum: a promising mushroom for antitumor and immunomodulating activity. Phytother. Res., 22, 614–619 (2008).
Kerzic, P. J., Pyatt, D. W., Zheng, J. H., Gross, S. A., Le, A., and Irons, R. D., Inhibition of NF-kappaB by hydroquinone sensitizes human bone marrow progenitor cells to TNF-alpha-induced apoptosis. Toxicology, 187, 127–137 (2003).
Kim, E. H., Lee, M. J., Kim, I. H., Pyo, S., Choi, K. T., and Rhee, D. K., Anti-apoptotic effects of red ginseng on oxidative street induced by hydrogen peroxide in SK-NSH cells. J. Ginseng Res., 34, 138–144 (2010a).
Kim, H. D., Ha, S. E., Kang, J. R., and Park, J. K., Effect of Korean red Ginseng extract on cell death responses in peroxyritrite-treated keratinocytes. J. Ginseng Res., 34, 205–211 (2010b).
Kim, J. Y., Byeon, S. E., Lee, Y. G., Lee, J. Y., Park, J., Hong, E. K., and Cho, J. Y., Immunostimulatory activities of polysaccharides from liquid culture of pine-mushroom Tricholoma matsutake. J. Microbiol. Biotechnol., 18, 95–103 (2008).
Kodama, N., Komuta, K., and Nanba, H., Effect of Maitake (Grifola frondosa) D-Fraction on the activation of NK cells in cancer patients. J. Med. Food, 6, 371–377 (2003).
Kodani, S., Hayashi, K., Hashimoto, M., Kimura, T., Dombo, M., and Kawagishi, H., New sesquiterpenoid from the mushroom Sparassis crispa. Biosci. Biotechnol. Biochem., 73, 228–229 (2009).
Lee, H. M., Surh, B. Y., and Chun, Y. J., Roles of neutral sphingomyelinase 1 on CD95-mediated apoptosis in human Jurkat T lymphocytes. Biomol. Ther., 18, 262–270 (2010).
Lee, Y. G., Lee, W. M., Kim, J. Y., Lee, J. Y., Lee, I. K., Yun, B. S., Rhee, M. H., and Cho, J. Y., Src kinase-targeted antiinflammatory activity of davallialactone from Inonotus xeranticus in lipopolysaccharide-activated RAW264.7 cells. Br. J. Pharmacol., 154, 852–863 (2008).
Lee, Y. G., Chain, B. M., and Cho, J. Y., Distinct role of spleen tyrosine kinase in the early phosphorylation of inhibitor of kappaB alpha via activation of the phosphoinositide-3-kinase and Akt pathways. Int. J. Biochem. Cell Biol., 41, 811–821 (2009).
Linton, M. F. and Fazio, S., Macrophages, inflammation, and atherosclerosis. Int. J. Obes. Relat. Metab. Disord., 27Suppl 3, S35–S40 (2003).
Maynard, M. A. and Ohh, M., The role of hypoxia-inducible factors in cancer. Cell. Mol. Life Sci., 64, 2170–2180 (2007).
Nameda, S., Harada, T., Miura, N. N., Adachi, Y., Yadomae, T., Nakajima, M., and Ohno, N., Enhanced cytokine synthesis of leukocytes by a beta-glucan preparation, SCG, extracted from a medicinal mushroom, Sparassis crispa. Immunopharmacol. Immunotoxicol., 25, 321–335 (2003).
Niu, Y. C., Liu, J. C., Zhao, X. M., Su, F. Q., and Cui, H. X., Immunostimulatory activities of a low molecular weight antitumoral polysaccharide isolated from Agaricus blazei Murill (LMPAB) in Sarcoma 180 ascitic tumor-bearing mice. Pharmazie, 64, 472–476 (2009).
Ohno, N., Miura, N. N., Nakajima, M., and Yadomae, T., Antitumor 1,3-beta-glucan from cultured fruit body of Sparassis crispa. Biol. Pharm. Bull., 23, 866–872 (2000).
Park, H. G., Shim, Y. Y., Choi, S. O., and Park, W. M., New method development for nanoparticle extraction of watersoluble beta-(1→3)-D-glucan from edible mushrooms, Sparassis crispa and Phellinus linteus. J. Agric. Food Chem., 57, 2147–2154 (2009).
Song, H., Kim, H., Jung S., and Lee, D. H., Characterization of tunicamycin as anti-obesity agent. Biomol. Ther., 17, 162–167 (2009).
Tada, R., Harada, T., Nagi-Miura, N., Adachi, Y., Nakajima, M., Yadomae, T., and Ohno, N., NMR characterization of the structure of a beta-(1→3)-D-glucan isolate from cultured fruit bodies of Sparassis crispa. Carbohydr. Res., 342, 2611–2618 (2007).
Vogel, S., Hirschfeld, M. J., and Perera, P. Y., Signal integration in lipopolysaccharide (LPS)-stimulated murine macrophages. J. Endotoxin Res., 7, 237–241 (2001).
Yadav, M. and Schorey, J. S., The beta-glucan receptor dectin-1 functions together with TLR2 to mediate macrophage activation by mycobacteria. Blood, 108, 3168–3175 (2006).
Yamamoto, K., Kimura, T., Sugitachi, A., and Matsuura, N., Anti-angiogenic and anti-metastatic effects of beta-1,3-D-glucan purified from Hanabiratake, Sparassis crispa. Biol. Pharm. Bull., 32, 259–263 (2009).
Zjawiony, J. K., Biologically active compounds from Aphyllophorales (polypore) fungi. J. Nat. Prod., 67, 300–310 (2004).
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Lee, S.Y., Lee, Y.G., Byeon, S.E. et al. Mitogen activated protein kinases are prime signalling enzymes in nitric oxide production induced by soluble β-glucan from Sparassis crispa . Arch. Pharm. Res. 33, 1753–1760 (2010). https://doi.org/10.1007/s12272-010-1107-3
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DOI: https://doi.org/10.1007/s12272-010-1107-3