Differential regulation by fucoidan of IFN-γ-induced NO production in glial cells and macrophages.
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.
Do
Hang
H
Division of Immunopharmacology, College of Pharmacy, Sungkyunkwan University, Kyunggi-do 440-746, Republic of Korea.
Kang
Nam-Sung
NS
Pyo
Suhkneung
S
Billiar
Timothy R
TR
Sohn
Eun-Hwa
EH
D000818:Animals; D000970:Antineoplastic Agents; D002460:Cell Line; D007371:Interferon-gamma / Q000502:physiology*; D053613:Janus Kinase 1 / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000378:metabolism*; D051379:Mice; D009457:Neuroglia / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D011134:Polysaccharides / Q000494:pharmacology*; D051381:Rats; D050791:STAT Transcription Factors / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000970:Antineoplastic Agents; D011134:Polysaccharides; D050791:STAT Transcription Factors; D009569:Nitric Oxide; D007371:Interferon-gamma; C007789:fucoidan; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D053613:Janus Kinase 1; D048051:p38 Mitogen-Activated Protein Kinases