Fucoidan regulates IFN‐γ–induced NO and iNOS production differently in C6 glioma cells and RAW264.7 cells: the involvement of JAK/STAT, p38 activation and TNF‐α production

Abstract

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)).