We compared the abilities of alginate polymers having different molecular sizes and compositions to induce the secretion of tumor necrosis factor (TNF)-α in RAW264.7 cells. The molecular sizes and α-L-guluronate/ β-D-mannuronate (M/G) ratios of highly purified alginate polymers used in this study were 9000-38∈000 and 1.50-3.17, respectively. Among the alginates tested, I-S, which had the highest molecular weight, showed the most potent TNF-α-inducing activity. The M/G ratio also seemed to influence this activity, and, among alginates with similar molecular sizes, alginates with a higher M/G ratio tended to show higher activity. Interestingly, the enzymatic depolymerization of I-S with bacterial alginate lyase resulted in a dramatic increase in the TNF-α-inducing activity. Such an effect of enzymatic digestion was also observed in a relatively low-molecular-weight alginate (ULV-3), which originally had very low TNF-α-inducing activity. Furthermore, the inhibition profiles of the TNF-α-inducing activity of enzymatically digested I-S shown by three specific mitogen-activated protein (MAP) kinase inhibitors differed from those of intact I-S. These results suggest that the underlying mechanism of the TNF-α-inducing activity of enzymatically depolymerized alginate oligomers is not necessarily the same as that of original alginate polymer.
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