In neurodegenerative disorders activated glial cells overproduce NO and iNOS, which causes neurotoxicity. Here, we examined the action of fucoidan on TNF‐α and IFN‐γ(T/I‐) induced NO production in C6 cells. Fucoidan suppressed T/I‐induced NO production and iNOS expression. In addition, fucoidan inhibited T/I‐induced AP‐1, IRF‐1, and p38 MAPK activation and induced SR‐B1 expression. Blocking of SR‐B1 didn't reverse the inhibitory effect of fucoidan on T/I‐ stimulated NO production. However, inhibition of SR‐B1 expression by siRNA increased iNOS expression and p38‐p in T/I‐stimulated C6. Also, fucoidan directly increased SR‐B1 expression and which was associated with p38 MAPK activation. Overall, p38 MAPK, AP‐1, and IRF‐1 play an important role in the inhibitory effect of fucoidan on T/I‐stimulated NO production, and intracellular SR‐B1 expression may be related to the inhibition of iNOS expression by fucoidan via regulation of p38‐p. Fucoidan could be a potential therapeutic agent for treating inflammatory‐related neuronal injury in neurological disorders.(This work was supported by grant No. RTI05‐01‐02 from the Regional Technology Innovation Program of the Ministry of Konwledge Economy(MKE))
It has been shown that glial cells and macrophages have many both similar and different characteristics including signalings responsible for production of NO. In the present study, we examined the effect of fucoidan on NO and iNOS production induced by TNF‐α and IFN‐γ, comparing between Raw264.7 and C6 cells. Our data shows that fucoidan affects only IFN‐γ‐induced iNOS but not TNF‐α‐induced iNOS in both cells. Elucidating mechanisms underlying effect of fucoidan on IFN‐γ signaling, we found that fucoidan inhibited IFN‐γ‐induced iNOS expression in C6 cells via inhibition of JAK/STAT and p38 activation. In contrast, in Raw264.7, fucoidan increased IFN‐γ‐induced iNOS via increase TNF‐α production which is negatively regulated by p38. We also found that the effect of fucoidan on Raw264.7 was not mediated by SR‐A1, a well‐known receptor of fucoidan, suggesting the involvement of other receptors. Our data, therefore, show the marked difference between glial cells and macrophages in response to fucoidan which should be considered in clinical using of fucoidan (This work was supported by grant No. RTI05‐01‐02 from the Regional Technology Innovation Program of the Ministry of Konwledge Economy(MKE)).
The β‐glucan receptor dectin‐1 may contribute to phagocytosis. Coriolus versicolor has been known to have immunomodulatory effects. For further understanding of the phagocytic activity and mechanisms for β‐glucan from C. versicolor, we examined phagocytosis, NO and NOS production in β‐glucan‐treated macrophages by dectin‐1 antagonist, laminarin. It showed that the treatment of β‐glucan induced a remarkable increase of phagocytosis in RAW264.7 cells, peritoneal macrophages and microglia. However, the activity of β‐glucan‐induced phagocytosis was abrogated by the pre‐treatment of laminarin. We also examined whether NO production and NOS expression are involved in phagocytosis and β‐glucan induced dectin‐1 signal pathways. Our results showed that phagocytic activity was not increased in the presence of iNOS inhibitor, S‐methylisothiourea, cNOS inhibitor and diphenylene iodonium chloride in the β‐glucan‐treated cells. The role of Ikaros in regulating phagocytic effects of β‐glucan were also determined. Taken together, these results suggest that β‐glucan enhances phagocytosis via dectin‐1 signal pathways and these effects of β‐glucan might be related to NO, cNOS, iNOS and Ikaros regulation.
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