Differential Regulation by Fucoidan of IFN-γ-Induced NO Production in Glial cells and Macrophages

초록

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-gamma 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-gamma-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-gamma-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 or NO/iNOS production. In RAW264.7 cells, fucoidan enhanced p38 activation and induced TNF-alpha 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-gamma-induced NO/iNOS production differently in brain and peritoneal macrophages due to the different roles of p38 but the effects on TNF-alpha production in the two cell types. These novel observations including selective and cell-type specific effects of fucoidan on IFN-gamma-mediatecl signaling and iNOS expression raise the possibility that it alters the sensitivity of cells to the p38 activation. J. Cell. Biochem. 111: 1337-1345, 2010. (C) 2010 Wiley-Liss, Inc.

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