Activation of murine peritoneal macrophages by sulfated exopolysaccharide from marine microalga Gyrodinium impudicum (strain KG03): involvement of the NF-κB and JNK pathway.

Abstract

This study examined the ability of microalgal sulfated exopolysaccharide (MSE) from marine microalga Gyrodinium impudicum (strain KG03) to induce secretory and cellular responses in murine peritoneal macrophages. The cytotoxicity induced by preincubating tumor cells with MSE was demonstrated to be concentration-dependent. The MSE-induced tumoricidal activity was partially abrogated by a NO inhibitor, whereas the anti-TNF-？and anti-IFN-？/？antibodies as well as the scavengers of reactive oxygen intermediates had no effect. In addition, supernatants from murine peritoneal macrophages treated with MSE contained nitrite and their iNOS enzymatic activity was significantly increased. Therefore, the tumoricidal activity induced by MSE appeared to be mediated by the production of NO. Treating the macrophages with a JNK inhibitor (SP600125) partially blocked the tumoricidal activation and NO production induced by MSE, whereas inhibitors of the other kinases did not have an inhibitory effect. These results suggest that MSE induces NO production via the JNK dependent pathway. Furthermore, electrophoretic mobility shift assay analyses revealed that the MSE treatment induced the activation of the NF-κB transcription factor. Overall, these results indicate that the tumoricidal activity induced by MSE is mainly due to NO production, and the activation of macrophage by MSE is mediated probably via the NF-kB and JNK pathway.