Structure-activity relationship of alginate oligosaccharides in the induction of cytokine production from RAW264.7 cells

Mami Iwamoto, Maki Kurachi, Takuji Nakashima, Daekyung Kim, Kenichi Yamaguchi, Tatsuya Oda*, Yoshiko Iwamoto, Tsuyoshi Muramatsu


研究成果: Article査読

201 被引用数 (Scopus)


Guluronate and mannuronate oligomers with various degree of polymerization were prepared from polyguluronate (PG) and polymannuronate (PM) with an alginate lyase from a Pseudoalteromonas sp., and their activities to induce cytokine secretion from mouse macrophage cell line RAW264.7 cells were examined. Enzymatically depolymerized unsaturated alginate oligomers induced tumor necrosis factor (TNF)-α secretion from RAW264.7 cells in a structure-depending manner, while the activities of saturated alginate oligomers prepared by acid hydrolysis were fairly low or only trace levels. These results suggest that unsaturated end-structure of alginate oligomers was important for the TNF-α-inducing activity. Among the unsaturated guluronate (G3-G9) and mannuronate (M3-M9) oligomers, G8 and M7 showed the most potent activity, respectively. Bio-Plex assay revealed that interleukin (IL)-1α, IL-1β, and IL-6 secretion from RAW264.7 cells were also induced by unsaturated alginate oligomers with similar structure-activity relationship profiles as seen in TNF-α, and the most potent activities were observed with G8 and M7. These results suggest that G8 and M7 may have the most suitable molecular size or entire structural conformation as stimulant for cytokine secretion. Since antibodies to Toll-like receptor (TLR)2 and TLR4 effectively inhibited the G8- and M7-induced production of TNF-α, these alginate oligomers may stimulate innate immunity through the pattern recognition receptors on macrophages similar to microbial products.

ジャーナルFEBS Letters
出版ステータスPublished - 2005 8月 15

ASJC Scopus subject areas

  • 生物理学
  • 構造生物学
  • 生化学
  • 分子生物学
  • 遺伝学
  • 細胞生物学


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