Structure-Activity Relationship of (1→3)-β-D-Glucans in the Induction of Cytokine Production from Macrophages, in Vitro
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概要
- 論文の詳細を見る
In a previous study, we reported that one of the gel-forming (1→3)-β-D-glucans, grifolan (from Grifola frondosa, GRN), stimulated cytokine production from macrophages in vitro. However, several other gel-forming (1→3)-β-D-glucans, such as sonifilan (SPG) and SSG, did not induce cytokine production from macrophages. The ultrastructure of gel-forming (1→3)-β-D-glucans, especially the triple-and single-helix, does not affect the cytokine-inducing activity. The action on tumor necrosis factor α (TNFα) release was correlated with the molecular weight of GRN, since the highest molecular weight fraction of GRN, Mr≧450000,exhibited the strongest activity. Although, native SSG (Mr≧2000000) did not induce cytokine production, chemical modification involving debranching of the side chain glucosyl residues of SSG resulted in TNFα inducing activity. These results suggest that the branching ratio and molecular weight of (1→3)-β-D-glucans are important factors for the production of cytokines from macrophages. GRN-inducible TNFα release was reduced by co-culturing with SPG, SSG, or the soluble β-glucan, laminarin (LAM). Pretreatment alone with SPG or LAM was not sufficient for significant inhibition of GRN-inducible TNFα release. TNFα production induced with 50μg/ml of zymosan (ZyM) was also reduced by addition of SPG, but TNFα production, stimulated with a higher concentration (100μg/ml) of ZyM or with lipopolysaccharide (LPS), was not reduced significantly. The inhibitory effect of LAM on the uptake of GRN by RAW264.7 cells was not completely correlated with TNFα release. These results suggest that macrophages may incorporate β-glucans through certain (1→3)-β-D-glucan-specific mechanisms and/or other endocytosis pathways, and that the β-glucan-specific route is partially associated with cytokine production. In conclusion, TNFα release by macrophages is induced only by β-glucans with high molecular weights and lower branching ratios, and the mechanism for the recognition of β-glucans is multiple and assumed to be divided into several parts involving various cellular functions.
- 社団法人日本薬学会の論文
- 1995-10-15
著者
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大野 尚仁
東京薬科大学薬学部免疫学教室
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大野 尚仁
Laboratory of Immunopharmacology of Microbial Products, Tokyo University of Pharmacy and Life Scienc
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安達 禎之
Laboratory of Immunopharmacology of Microbial Products, Tokyo University of Pharmacy and Life Scienc
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宿前 利郎
Laboratory of Immunopharmacology of Microbial Products, Tokyo University of Pharmacy and Life Scienc
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宿前 利郎
東京薬科大学 薬 免疫
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宿前 利郎
東京薬科大学
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岡崎 光洋
Laboratory of Immunopharmacology of Microbial Products, School of Pharmacy, Tokyo University of Phar
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安達 禎之
東京薬科大学免疫学
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大野 尚仁
東京薬大免疫
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大野 尚仁
東京薬科大学免疫学
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大野 尚仁
帝京大学 医学部微生物学講座
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大野 尚仁
東京薬科大学
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大野 尚仁
東京薬科大学薬学部第一微生物学教室
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岡崎 光洋
Laboratory Of Immunopharmacology Of Microbial Products School Of Pharmacy Tokyo University Of Pharma
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安達 禎之
Laboratory Of Immunopharmacology Of Microbial Products Tokyo College Of Pharmacy
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Ohno N
Lab. Immunopharmacolgy Of Microbial Products Tokyo University Of Pharmacy And Life Science School Of
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