Abstract
Fucoidan has shown numerous biological actions; however, the molecular bases of these actions have being issued. We examined the effect of fucoidan on NO production induced by IFN-γ and the molecular mechanisms underlying these effects in two types of cells including glia (C6, BV-2) and macrophages (RAW264.7, peritoneal primary cells). Fucoidan affected IFN-γ-induced NO and/or iNOS expression both in macrophages and glial cells but in a contrast way. Our data showed that in C6 glioma cells both JAK/STAT and p38 signaling positively regulated IFN-γ-induced iNOS, which were inhibited by fucoidan. In contrast, in RAW264.7 cells JAK/STAT is a positive regulator whereas p38 is a negative regulator of NO/iNOS production. In RAW264.7 cells, fucoidan enhanced p38 activation and induced TNF-α production. We also confirmed the dual regulation of p38 in BV-2 microglia and primary peritoneal macrophages. From these results, we suggest that fucoidan affects not only IFN-γ-induced NO/iNOS production differently in brain and peritoneal macrophages due to the different roles of p38 but the effects on TNF-α production in the two cell types. These novel observations including selective and cell-type specific effects of fucoidan on IFN-γ-mediated signaling and iNOS expression raise the possibility that it alters the sensitivity of cells to the p38 activation.
Original language | English |
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Pages (from-to) | 1337-1345 |
Number of pages | 9 |
Journal | Journal of Cellular Biochemistry |
Volume | 111 |
Issue number | 5 |
DOIs | |
State | Published - 1 Dec 2010 |
Externally published | Yes |
Keywords
- IFN-γ
- fucoidan
- glia
- iNOS
- macrophage
- p38