Comparison of the activities of various alginates to induce TNF-alpha secretion in RAW264.7 cells.
We compared the abilities of alginate polymers having different molecular sizes and compositions to induce the secretion of tumor necrosis factor (TNF)-alpha in RAW264.7 cells. The molecular sizes and alpha-L-guluronate/beta-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-alpha-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-alpha-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-alpha-inducing activity. Furthermore, the inhibition profiles of the TNF-alpha-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-alpha-inducing activity of enzymatically depolymerized alginate oligomers is not necessarily the same as that of original alginate polymer.
Kurachi
Maki
M
Division of Biochemistry, Faculty of Fisheries, Nagasaki University, Japan. t-oda@net.nagasaki-u.ac.jp
Nakashima
Takuji
T
Miyajima
Chihiro
C
Iwamoto
Yoshiko
Y
Muramatsu
Tsuyoshi
T
Yamaguchi
Kenichi
K
Oda
Tatsuya
T
D000464:Alginates / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D000464:Alginates; D014409:Tumor Necrosis Factor-alpha; D020928:Mitogen-Activated Protein Kinases