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

Abstract:

: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)-alpha 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-alpha-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)-1alpha, IL-1beta, 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-alpha, 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-alpha, these alginate oligomers may stimulate innate immunity through the pattern recognition receptors on macrophages similar to microbial products.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Iwamoto M,Kurachi M,Nakashima T,Kim D,Yamaguchi K,Oda T,Iwamoto Y,Muramatsu T

doi

10.1016/j.febslet.2005.07.007

keywords:

subject

Has Abstract

pub_date

2005-08-15 00:00:00

pages

4423-9

issue

20

eissn

0014-5793

issn

1873-3468

pii

S0014-5793(05)00846-X

journal_volume

579

pub_type

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